Thyroid tumors identified

ABSTRACT

The invention relates to methods and kits for detecting thyroid cancer by detecting differences in the expression of genes that are differentially expressed in thyroid cancer cells.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent claims the benefit of priority, under 35 U.S.C. Section 119(e), to U.S. Provisional Patent Application Ser. No. 61/191,845 filed on Sep. 12, 2008, and U.S. Provisional Patent Application Ser. No. 61/207,812 filed Feb. 17, 2009, the contents of both of which applications are specifically incorporated by reference herein in their entireties.

FIELD OF THE INVENTION

The invention relates to detection and diagnosis of thyroid cancer. In some embodiments, the methods of the invention can be used to distinguish between benign thyroid cells or tissues, malignant thyroid cells or tissues, and follicular adenomas with nuclear atypia (FANA).

BACKGROUND OF THE INVENTION

Thyroid nodules are common in the United States, occurring in greater than 60% of individuals. Moreover, their incidence is steadily increasing, mainly because of the increased detection of smaller, asymptomatic nodules. Although the majority of these nodules are benign, a significant numbers of patients undergo surgical excision. Upon pathologic review of such thyroid tumors, clear-cut benign or malignant diagnoses often can be rendered. However, follicular lesions of the thyroid often pose a diagnostic challenge.

A particular diagnostic dilemma is presented in a subset of encapsulated follicular lesions with partial nuclear features of papillary thyroid carcinoma (PTC) (occasional nuclear grooves, focal nuclear clearing, and overlapping nuclei) and with histological features that fail to place them reliably in either the benign category or the malignant category. In the inventors' experience, these tumors represent approximately 10% of all follicular-patterned lesions observed at surgical pathology (see also, Arora et al. World J. Surg. 32:1237-1246 (2008)). The difficulty of classifying this group of tumors is exemplified further by several studies in which poor inter-observer agreement was demonstrated among expert endocrine pathologists ranging from 39% to 58% when they reviewed follicular-patterned lesions of the thyroid (Chan et al., Am J Clin Pathol. 117:16-18 (2002); Franc et al., Hum Pathol. 34:1092-1100 (2003); Lloyd et al., Am J Surg Pathol. 28:1336-1340 (2004); Saxen et al. Acta Pathol Microbiol Scand [A]. 1978; 86A:483-4864-8 (1978); Hirokawa et al. Am J Surg Pathol. 26:1508-1514 (2002)). This diagnostic difficulty in classifying such borderline tumors with standard terminology led Williams to propose the term well differentiated tumor of uncertain malignant potential (WDT-UMP) as a separate diagnostic category (Int J Surg Pathol. 8:181-183 (2000).

No matter what terminology is used for these tumors, additional tools are needed to determine whether thyroid nodules and/or tumors are actually malignant or simply benign, and/or whether such nodules and/or tumors can progress to become malignant tumors.

SUMMARY OF THE INVENTION

The invention relates to methods for improved diagnosis of thyroid cancer that can distinguish not only benign nodules from malignant thyroid tumors but can also identify borderline, pre-cancerous tumors (e.g., encapsulated follicular lesions that may have partial nuclear features of PTC) that may not need aggressive treatment. For example, in one study conducted by the inventors using the methods described herein, the majority of histologically uncertain tumors (66.7%) were determined to be premalignant tumors, while a smaller number of tumors were determined to be benign tumors (26.7%) and only a even smaller number of tumors were actually malignant tumors (6.7%). By using the methods and kits of the invention, the malignant thyroid tumors can be identified with greater certainty, thereby avoiding unnecessary, expensive and invasive medical procedures that might otherwise have been used to treat histologically uncertain tumors.

Thus, one aspect of the invention is a method of detecting whether thyroid cancer cells are present in a test tissue or cell sample which comprises (a) observing test levels of RNA or protein expression in the test tissue or cell sample for any differentially expressed gene, and (b) comparing the test levels of expression to one or more standard or control levels of expression, to ascertain whether higher or lower levels of expression of any of the genes is present in the test tissue or cell sample, and thereby detecting whether thyroid cancer cells are present in the test tissue or cell sample; wherein the differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof.

In some embodiments, the differentially expressed gene can be selected from the group consisting of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 and a combination thereof. In other embodiments, the differentially expressed gene can be selected from the group consisting of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, TIAM1 and a combination thereof. In further embodiments, the differentially expressed gene can be selected from the group consisting of C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 and a combination thereof.

Any methods available to one of skill in the art can be used to detect and/or quantify the test levels of RNA. For example, the test levels of RNA expressed can be detected by microarray analysis or by nucleic acid amplification. In some embodiments, the test levels of RNA expressed are detected by microarray analysis that includes use of one or more probes on the microarray that can hybridize to one or more of the differentially expressed genes, or an RNA or DNA copy of the one or more differentially expressed genes. For example, such methods can employ one or more probes that can hybridize to any of SEQ ID NO:119-172. In some embodiments, the one or more probes hybridize to one or more of the differentially expressed genes, or an RNA or DNA copy of the one or more differentially expressed genes under moderate to highly stringent hybridization conditions. For example, the hybridization conditions can be highly stringent hybridization conditions.

In other embodiments, nucleic acid amplification can be employed. Such nucleic acid amplification can include reverse transcription polymerase chain reaction, real time polymerase chain reaction, or quantitative polymerase chain reaction. For example, the test levels of RNA expressed can be detected by nucleic acid amplification using one or more primers that hybridize to one or more of the differentially expressed genes, or an RNA or DNA copy of the one or more differentially expressed genes under moderate to highly stringent hybridization conditions. The one or more primers employed can, for example, hybridize to any of SEQ ID NO:119-172. Such hybridization conditions can in some instances be highly stringent hybridization conditions.

The one or more standard or control levels of expression can include: an expression level observed for a malignant thyroid cancer cell or tissue; an expression level observed for a benign thyroid cell or tissue; an expression level observed for a follicular adenoma with nuclear atypia; an expression level observed for a borderline thyroid cell or tissue; an expression level observed for a normal non-cancerous thyroid cell or tissue; or an expression level observed for a constitutively expressed gene.

These methods can distinguish between benign, malignant and borderline thyroid cells or tissues. For example, these methods can distinguish between benign thyroid cells or tissues, malignant thyroid cells or tissues, and follicular adenomas with nuclear atypia (FANA). For example, the test tissue or cell sample is obtained from a patient with thyroid cancer or suspected of having thyroid cancer.

Another aspect of the invention is a kit comprising: (a) at least one set of oligonucleotide primers, wherein a first primer in the set contains a sequence complementary to a region in one strand of a nucleic acid sequence template and primes the synthesis of a first extension product, and a second primer contains a sequence complementary to a region in said first extension product and primes the synthesis of a nucleic acid strand complementary to said first extension product, and wherein the template is a differentially expressed gene, or an RNA or DNA copy of the differentially expressed gene; and (b) instructions for using the at least one set of oligonucleotide primers; wherein the differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof.

In some embodiments, the differentially expressed gene can be selected from the group consisting of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 and a combination thereof. In other embodiments, the differentially expressed gene can be selected from the group consisting of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, TIAM1 and a combination thereof. In further embodiments, the differentially expressed gene can be selected from the group consisting of C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 and a combination thereof. The first primer and/or the second primer can include a label. A container of nucleotides can also be included in the kit where the nucleotides are used as subunits in the synthesis of and amplified product. For example, the nucleotides can be ribonucleotides and/or deoxyribonucleotides. One or more of such nucleotides can include a label.

The instructions can describe a method for amplifying an mRNA, cRNA or cDNA corresponding to the differentially expressed gene(s). In some embodiments, the first primer and/or the second primer may hybridize to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene under moderate to highly stringent hybridization conditions. For example, the hybridization conditions can be highly stringent hybridization conditions in some instances.

Another aspect of the invention is a kit that includes (a) a microarray with covalently attached probes that can hybridize to a differentially expressed gene selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof; and (b) instructions for using the microarray.

In some embodiments, the differentially expressed gene can be selected from the group consisting of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 and a combination thereof. In other embodiments, the differentially expressed gene can be selected from the group consisting of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, TIAM1 and a combination thereof. In further embodiments, the differentially expressed gene can be selected from the group consisting of C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 and a combination thereof. Such probes can, in some embodiments, hybridize to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene, for example, under moderate to highly stringent hybridization conditions. In some embodiments, the hybridization conditions are highly stringent hybridization conditions. Such a kit can also include one or more standard or control probes. For example, the kit can include one or more probes for a constitutively expressed gene.

Another aspect of the invention is a method of detecting a mutation in a human BRAF gene that includes: (a) obtaining a test sample of genomic DNA from a human; (b) amplifying a segment of BRAF DNA from the genomic DNA using primers with SEQ ID NO: 1 and SEQ ID NO:2; and (c) detecting whether the mutation exists in the segment amplified; wherein the mutation consists of a glutamate substituted for valine at codon 600.

Such a method can also include detecting or confirming whether the human has thyroid cancer by observing test levels of RNA or protein expression in the test tissue or cell sample for any of the differentially expressed genes described herein, using any of the methods and/or kits described herein.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is an image of a histologically borderline lesion. Note the follicular architecture with focal nuclear clearing and occasional nuclear grooves.

FIG. 2 is a graphic generated by an unsupervised hierarchical cluster analysis. FA indicates follicular adenoma; HYP, hyperplastic lesion; BOR, borderline tumor; FVPTC, follicular variant of papillary thyroid carcinoma; PTC, papillary thyroid carcinoma.

FIG. 3 is a graphic generated by a 2-group K-means cluster analysis. FA indicates follicular adenoma; BOR, borderline tumor; FVPTC, follicular variant of papillary thyroid carcinoma; PTC, papillary thyroid carcinoma; HYP, hyperplastic lesion.

FIG. 4 is graphic generated by three-group K-means cluster analysis that identified 3 distinct groups of tumors based upon their gene expression patterns: malignant (left), benign (center), and intermediate (right). BOR indicates borderline tumor; FVPTC, follicular variant of papillary thyroid carcinoma; PTC, papillary thyroid carcinoma; FA, follicular adenoma; HYP, hyperplastic lesion.

FIG. 5 shows a Venn diagram illustrating the differentially expressed genes relating 61 genes to benign, borderline, and malignant tumors.

FIG. 6 is a schematic diagram showing proposed gene expression changes during tumorigenesis of follicular-patterned lesions of the thyroid.

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to methods of detecting malignant thyroid tumors and/or distinguishing whether thyroid tumors are benign, malignant, and/or pre-cancerous borderline tumors. While currently available histological and/or cytological procedures can sometimes distinguish benign and malignant thyroid tumors, there are many thyroid tumors that cannot readily be classified as either malignant or benign by such histological procedures. Patients with such unclassified tumors are often aggressively treated as though their tumors were malignant. However, by employing the methods and kits described herein, these unclassified tumors can be properly identified as either benign, malignant, or pre-cancerous borderline tumors, thereby reducing the need for expensive, invasive and unpleasant medical treatment when it is unnecessary.

The application describes an analysis of fifty histologically-unequivocal benign and malignant tumors, which led to the identification of a list of sixty-one genes that are differentially expressed in benign and malignant thyroid tumors. These differentially expressed genes are listed in Table 1.

By using probes for the fifty to sixty differentially expressed genes described herein, forty additional tumors were evaluated, including 15 histologically intermediate tumors, 11 benign tumors, and 14 papillary thyroid carcinomas (PTCs). Differential gene expression was used to detect whether the histologically intermediate thyroid tumors were malignant or not. As illustrated herein, the majority of histologically intermediate tumors (66.7%) were actually borderline, pre-malignant tumors that exhibited gene expression similarities with benign tumors (26.7%) and malignant tumors (6.7%) (FIG. 4). This third category of borderline tumors (encapsulated follicular tumors with cytological atypia) does not fit into previously proposed benign or malignant classification schemes using standard histological, immuno-histochemical, or mutation analyses. Instead, these borderline tumors are pre-malignant tumors that may warrant monitoring but do not generally need immediate aggressive medical treatment.

Twenty-seven genes were expressed differentially between the benign and borderline groups, including the cyclic AMP response element binding protein/p300-interactivator with glutamic acid/aspartic acid-rich carboxy-terminal domain 1 or CITED1 gene and the fibroblast growth factor receptor 2 or FGFR2 gene. Fourteen genes were expressed differentially between the borderline group and malignant tumors, for example, the met proto-oncogene and of the high-mobility group adenine/thymine-hook 2 or HMGA2 gene in malignancies. Mutations of the v-raf murine sarcoma viral oncogene homolog B1 or BRAF gene were identified in 4 of 14 malignant tumors but not in benign or borderline tumors.

Patients who had histologically or molecularly borderline tumors did not have metastasis or recurrences. These data indicate that encapsulated thyroid follicular lesions with partial nuclear features of PTC are biologically borderline tumors that are molecularly distinct from benign and malignant tumors. Moreover, the data indicate that such borderline tumors identified by the methods and kits of the invention are pre-cancerous with no immediate need for aggressive cancer treatment.

The gene expression profiling methods described herein are more accurate than existing procedures for diagnosing problematic thyroid tumors. For example, the methods of the invention can identify malignant thyroid tumors with greater than 90% sensitivity and 80% specificity. In some embodiments, the methods of the invention can identify malignant thyroid tumors with greater than 93% sensitivity and greater than 82% specificity.

DEFINITIONS

“Genes” are the units of heredity in living organisms. They are encoded in the organism's genetic material (DNA or RNA), and control the physical development and behavior of the organism. Genes encode the information necessary to construct the proteins (etc.) needed for the organism to function. The term “genes” generally refers to the region of DNA (or RNA, in the case of some viruses) that determines the structure of a protein (the coding sequence), together with the region of DNA that controls when and where the protein will be produced (the regulatory sequences).

As used herein, the phrase “expression profiling” refers to differential gene expression analysis/techniques. Examples of such techniques include microarray analyses, real time PCR and qPCR. Microarray technology allows for the comparison of gene expression between, for example, normal and diseased (e.g., cancerous) cells or cells which express different cell markers. There are several names for microarray technology including DNA microarrays, DNA arrays, DNA chips, gene chips, and others.

In this disclosure, “comprises,” “comprising,” “containing” and “having” and the like can have the meaning ascribed to them in U.S. Patent law and can mean “includes,” “including,” and the like; “consisting essentially of” or “consists essentially” likewise has the meaning ascribed in U.S. Patent law and the term is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not deleteriously changed by the presence of more than that which is recited.

Other definitions may appear throughout this disclosure in the appropriate context.

Genes that are Differentially Expressed in Benign and Malignant Thyroid Tumors

The expression levels of one or more of the genes listed in Table 1 can be detected using the methods and kits of the invention. In some embodiments, the expression levels of two or more, or three or more, or four or more, or five or more of the genes listed in Table 1 are detected to assess whether a thyroid nodule contains benign or malignant cancer cells. In other embodiments, the expression levels of seven or more, or eight or more, or ten or more, or twelve or more of the genes listed in Table 1 are detected to assess whether a thyroid nodule contains benign or malignant cancer cells. In further embodiments, the expression levels of no more than ten, no more than twelve, no more than fifteen, no more than twenty of the genes listed in Table 1 are detected to assess whether a thyroid nodule contains benign or malignant cancer cells.

Differential expression of these genes means that the mRNA or transcript levels produced by these genes increases or decreases in a test tissue or cell sample (e.g., a thyroid tissue biopsy) relative to a control, thereby indicating the presence of benign thyroid cells or tissues, malignant thyroid cells or tissues, and/or borderline tumors (e.g., encapsulated thyroid follicular lesions with partial nuclear features of PTC) in the test tissue or cell sample from which the RNA/transcripts were obtained.

Genes whose expression changes in thyroid tumor cells include one or more of the following genes: ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC4A4, SLC25A15, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, or a combination thereof.

The following genes were expressed at higher levels in malignant thyroid cancer tissues and cells than in benign thyroid lesions: CAPN3, CITED 1, DAPK2, DPP4, DUSP4, DTX4, GALNT7, HMGA2, IGFBP6, LRP4, MET, MYH10, PFAAP5, PROS1, PSD3, QPCT, RAB27A, RXRG, SERPINA1, SLIT1, SPTAN1, TIAM1, TIMP1, and UPP1. Thus, detection of an increase in the expression of one or more of these genes in a tissue or cell sample, relative to a benign control tissue sample, is indicative of thyroid cancer.

On the other hand, the following genes are expressed at lower levels in malignant thyroid cancer tissues than in benign thyroid lesions: ANK2, ARHGAP6, C11orf17, CDH16, CITED 2, COL9A3, ChGn, CKB, CSRP2, DIO1, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, HGD, KIT, MATN2, NAUK2, PGF, PIP3-E, PKNOX2, PRKACB, SDC4, SLC4A4, SLC25A15, TFCP2L1, TNS3, and TSPAN12. Thus, detection of a decrease in the expression of one or more of these genes in a tissue or cell sample, relative to a benign control tissue sample, is indicative of thyroid cancer.

However, as described herein, the inventors have discovered a third type of thyroid tumor that is pre-cancerous and may not need aggressive medical treatment when initially detected. As described herein, these borderline tumors can be distinguished from benign and malignant by their expression patterns.

The following genes are differentially expressed between malignant and borderline/benign tumors: DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, and/or UPP1. Each of these genes exhibit increased expression in malignant tumors relative to borderline and benign tumors, except DIO1, SDC4, and SLC4A4, which are expressed at lower levels in malignant thyroid tissues and cells when compared to their expression in benign and borderline tumors. Thus, when differential expression of one or more of these genes is detected in a thyroid test or cell sample, such differential expression is indicative of the presence of malignant tumor cells.

The following genes are differentially expressed between benign and borderline/malignant lesions: ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, and/or TIAM1. Each of these genes exhibit decreased expression in malignant tumors relative to borderline/malignant tumors, except CITED 1, DUSP4, LRP4, PSD3, SLIT1, SPTAN1, and TIAM1, which are expressed at higher levels in malignant tissues and cells compared to borderline/malignant tissues and cells. Thus, benign thyroid lesions can be identified and distinguished from borderline/malignant tumors by their differential expression patterns in a thyroid test tissue or cell sample.

The following genes are differentially expressed between benign and malignant lesions: C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15. Each of these genes are expressed at higher levels in malignant thyroid tumors relative to their expression levels in benign thyroid lesions, except the following genes: C11orf17, CKB, CSRP2, HGD, PGF, PKNOX2, PRKACB, and SLC25A15, which are expressed at lower levels in malignant thyroid tissues relative to benign thyroid lesions. Thus, to definitively distinguish between benign and malignant thyroid tissues, the expression of these genes can be evaluated.

The difference in expression levels between a differentially expressed gene in malignant thyroid tissues relative to the expression levels for that gene in a control (e.g., normal thyroid tissues) can be at least a 20% difference in expression levels, at least a 30% difference in expression levels, at least a 40% difference in expression levels, at least a 50% difference in expression levels, at least a 60% difference in expression levels, at least a 70% difference in expression levels, at least an 80% difference in expression levels, at least a 90% difference in expression levels, at least a 100% difference in expression levels, and/or a more than a 100% difference in expression levels. Thus, in some embodiments, the difference in expression levels between a differentially expressed gene in malignant thyroid tissues relative to the expression levels for that gene in a control (e.g., normal thyroid tissues) can be at least 1.5 fold, at least 1.7 fold, at least 1.8 fold, at least 2-fold, at least 2.2 fold, at least at least 2.3 fold, at least 2.4 fold, at least 2.5 fold, or more than 2.5 fold. Table 1 provides examples of the differences in expression levels that can readily be determined and observed.

Gene expression data may be gathered in any way that is available to one of skill in the art. For example, gene expression levels can be detected and quantified by employing an array of probes that hybridize to the different transcripts of one or more of the genes listed in Table 1, by using nucleic acid amplification (e.g., quantitative polymerase chain reaction) and through nucleic acid hybridization procedures. Other methods of determining expression of the genes include traditional Northern blotting, nuclease protection, RT-PCR and differential display methods can be used for detecting gene expression levels. Such methods are described in the following sections and in the Examples.

Probes and primers that can hybridize to an RNA, cDNA corresponding to any of the following genes can be used to detect differential gene expression: ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC4A4, SLC25A15, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, or a combination thereof.

Sequences for these differentially expressed genes are available and can be used to make probes and primers for detecting expression levels. Examples of sequences that can be used to make probes and primers for these are provided hereinbelow. Any probe or primer that can hybridize to an RNA or cDNA of any of these genes can be used in the methods of the invention. In some embodiments, such a probe or primer hybridizes such to an RNA or cDNA of a differentially expressed gene under moderately stringent conditions. In other embodiments, such a probe or primer hybridizes such to an RNA or cDNA of a differentially expressed gene under highly stringent conditions. Such conditions are known to one of skill in the art and are described herein.

RNA Manipulation

One of skill in the art will appreciate that in order to assess the mRNA transcript levels (and thereby the expression levels) of a gene or genes, it is desirable to provide a RNA sample or a nucleic acid sample derived from the mRNA transcript(s). As used herein, a nucleic acid derived from an mRNA transcript refers to a nucleic acid ultimately synthesized from the mRNA transcript. Thus, the original mRNA obtained from a test tissue or cell sample can serve as a template for generating a nucleic acid derived from an mRNA. For example, such a nucleic acid derived from an mRNA can be a cDNA reverse transcribed from an mRNA, an RNA transcribed from the cDNA, a DNA amplified from the cDNA, an RNA transcribed from the amplified DNA, and the like. Detection of such derived products is indicative of the presence and abundance of the original mRNA transcript in a test tissue or cell sample. Thus, suitable samples include, but are not limited to, mRNA transcripts of the gene or genes, cDNA reverse transcribed from the mRNA, cRNA transcribed from the cDNA, and the like.

Where it is desired to quantify the transcription level of one or more genes in a sample, the concentration of the mRNA transcript(s) of the gene or genes is proportional to the transcription level of that gene. Similarly, when hybridization is employed to quantify transcription levels, the hybridization signal intensity can be proportional to the amount of hybridized nucleic acid. As described herein, controls can be run to correct for variations introduced during sample preparation and/or hybridization.

The nucleic acid may be isolated from a test tissue or cell sample (and/or a control tissue sample) according to any of a number of methods well known to those of skill in the art. One of skill in the art will appreciate that where expression levels of a gene or genes are to be detected, RNA (mRNA) is isolated. Methods of isolating total mRNA are well known to those of skill in the art. For example, methods of isolation and purification of nucleic acids are described in Sambrook et al. (1989) MOLECULAR CLONING: A LABORATORY MANUAL, Cold Spring Harbor Laboratory Press; and Sambrook et al. (2001). MOLECULAR CLONING: A LABORATORY MANUAL (3rd ed.). Cold Spring Harbor Laboratory Press, which are both incorporated herein by reference in their entireties. Filter based methods for the isolation of mRNA are also available in the art and can be used for isolating mRNA from biological samples. Examples of commercially available filter-based RNA isolation systems include RNAqueous™ (Ambion) and RNeasy™ (Qiagen). One of skill in the art would appreciate that it is desirable to inhibit or destroy RNase present in homogenates of biological samples soon after obtaining the samples so that the mRNA is not degraded by nucleases during testing.

Frequently, it is desirable to amplify the nucleic acid sample prior to evaluation. If a quantitative result is desired care can be taken to use an amplification method that maintains or controls for the relative frequencies of the amplified nucleic acids.

Methods of “quantitative” amplification are well known to those of skill in the art. For example, quantitative PCR involves simultaneously co-amplifying a known quantity of an internal control nucleic acid. This provides an internal standard that may be used to calibrate the PCR reaction. Detection of the internal control sequence along with the mRNAs of interest (e.g., those from any of the genes in Table 1) allows one of skill in the art to monitor whether the mRNA isolation, purification and quantification procedures accurately reflect actual expression levels or whether there is a problem with any of these procedures (e.g., the mRNA has become degraded during one of the procedures).

Suitable amplification methods include, but are not limited to polymerase chain reaction (PCR) (Innis & Gelfand, Optimization of PCRs. In: PCR PROTOCOLS: A GUIDE TO METHODS AND APPLICATIONS (eds. M. A. Innis, et al.), pp. 3-12. Academic Press, San Diego (1990); ligase chain reaction (LCR) (see, Wu and Wallace, Genomics (1989)); Landegren, et al., Science 241: 1077-1080 (1988); Barringer, et al., Gene 89: 117-122 (1990); transcription amplification (Kwoh, et al., Proc. Natl. Acad. Sci. USA 86, 1173-1177 (1989)), and self-sustained sequence replication (Guatelli, et al., Proc. Natl. Acad. Sci. 87: 1874-1878 (1990)).

In one embodiment, a nucleic acid sample is the total mRNA isolated from a biological sample (e.g., a test tissue or cell sample). The term “biological sample,” as used herein, refers to a sample obtained from an organism or from components (e.g., cells) of an organism, including normal tissue (e.g., as a control) and diseased tissue such as a tumor, a neoplasia or a hyperplasia. The sample may be of any biological tissue or fluid or cells from any organism as well as cells raised in vitro, such as cell lines and tissue culture cells. The biological sample may also be referred to as a “clinical sample” derived from a patient. Such samples include, but are not limited to, tissue biopsy or fine needle aspiration biopsy samples, blood, blood cells (e.g., white cells), urine, peritoneal fluid, and pleural fluid, or cells therefrom. Biological samples may also include sections of tissues such as frozen sections or formalin fixed sections taken for histological purposes.

In some embodiments, the sample mRNA is reverse transcribed with a reverse transcriptase, such as SuperScript II (Invitrogen), and a primer consisting of an oligo-dT to generate first-strand cDNA. Other desirable sequences can be incorporated into the first-strand cDNA by linking those sequences onto the oligo-dT primer (e.g., a restriction site sequence, a sequence encoding a promoter such as a phage T7 promoter, etc.). A second-strand DNA is polymerized in the presence of a DNA polymerase, DNA ligase, and RNase H. The resulting double-stranded cDNA may be blunt-ended using T4 DNA polymerase and purified by phenol/chloroform extraction. The double-stranded cDNA can then be then transcribed into cRNA or amplified to generate a pool of amplified cDNAs. Methods for the in vitro transcription of RNA are known in the art and describe in, for example, Van Gelder, et al. (1990) and U.S. Pat. Nos. 5,545,522; 5,716,785; and 5,891,636, all of which are incorporated herein by reference.

If desired, a label may be incorporated into the cRNA or cDNA when it is transcribed. Those of skill in the art are familiar with methods for labeling nucleic acids. For example, the cRNA may be transcribed in the presence of biotin-ribonucleotides or the cDNA may be synthesized in the presence of biotin-deoxyribonucleotides. The BioArray High Yield RNA Transcript Labeling Kit (Enzo Diagnostics) is a commercially available kit for biotinylating cRNA.

It will be appreciated by one of skill in the art that the direct transcription method described above provides an antisense (aRNA) pool. Where antisense RNA is used with a microarray for detection, the antisense RNA can be the “target nucleic acid” that is hybridized to an array of the oligonucleotide probes provided in the microarray. In that case the oligonucleotide probes on the microarray are chosen to be complementary to subsequences of the antisense nucleic acids. Conversely, where the target nucleic acid pool is a pool of sense nucleic acids, the oligonucleotide probes are selected to be complementary to subsequences of the sense nucleic acids. Finally, where the nucleic acid pool is double stranded, the probes may be of either sense, or both senses, as the target nucleic acids include both sense and antisense strands.

To detect hybridization, it may be advantageous to employ nucleic acids in combination with an appropriate detection means. Recognition moieties incorporated into primers, incorporated into the amplified product during amplification, or attached to probes that can hybridize to the amplified product are useful in the identification of nucleic acid molecules. A number of different labels may be used for this purpose including, but not limited to, fluorophores, chromophores, radiophores, enzymatic tags, antibodies, chemiluminescence, electroluminescence, and affinity labels. One of skill in the art will recognize that these and other labels can be used with success in this invention.

Examples of affinity labels include, but are not limited to the following: an antibody, an antibody fragment, a receptor protein, a hormone, biotin, Dinitrophenyl (DNP), or any polypeptide/protein molecule that binds to an affinity label. Examples of enzyme tags include enzymes such as urease, alkaline phosphatase or peroxidase to mention a few. Colorimetric indicator substrates can be employed to provide a detection means visible to the human eye or spectrophotometrically, to identify specific hybridization with complementary nucleic acid-containing samples. Examples of fluorophores include, but are not limited to, Alexa 350, Alexa 430, AMCA, BODIPY 630/650, BODIPY 650/665, BODIPY-FL, BODIPY-R6G, BODIPY-TMR, BODIPY-TRX, Cascade Blue, Cy2, Cy3, Cy5, 6-FAM, Fluoroscein, HEX, 6-JOE, Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, REG, Rhodamine Green, Rhodamine Red, ROX, TAMRA, TET, Tetramethylrhodamine, and Texas Red.

Means of detecting such labels are well known to those of skill in the art. For example, radiolabels may be detected using photographic film or scintillation counters. In other examples, fluorescent markers may be detected using a photodetector to detect emitted light. In still further examples, enzymatic labels are detected by providing the enzyme with a substrate and detecting the reaction product produced by the action of the enzyme on the substrate, and colorimetric labels are detected by simply visualizing the colored label or by use of spectrometer.

So called “direct labels” are detectable labels that are directly attached to or incorporated into the target (sample) nucleic acid prior to hybridization to a probe or microarray. In contrast, so called “indirect labels” are joined to the hybrid duplex after hybridization. In some embodiments, the indirect label is attached to a binding moiety that has been attached to the target nucleic acid prior to the hybridization. Thus, for example, the target nucleic acid may be biotinylated before the hybridization. After hybridization, an avidin-conjugated fluorophore will bind the biotin-bearing hybrid duplexes providing a label that is easily detected. For a detailed review of methods of labeling nucleic acids and detecting labeled hybridized nucleic acids see, for example, Peter C. van der Vliet & Shiv Pillai, eds., LABORATORY TECHNIQUES IN BIOCHEMISTRY AND MOLECULAR BIOLOGY (1993).

Methods for Detecting Differential Expression

The present invention includes a method for detecting and/or quantifying expression of any combination of the genes listed in Table 1 (e.g., a target nucleic acid) in a biological sample.

Such detection and quantification methods can involve nucleic acid amplification (e.g., reverse transcription PCR, quantitative PCR and/or real-time PCR), wherein a sample containing a target nucleic acid that is to be amplified (e.g. a cDNA generated from an RNA sample by reverse transcription) is mixed with 1) primers that are complementary to sequences within the target sequence to be amplified, 2) a thermostable polymerase, and 3) four different nucleoside triphosphates. The normal steps of nucleic acid amplification are then followed—melting, annealing and synthesis—by thermal cycling of the mixture. The primers employed can be linked to a label. In some embodiments, a fluorescent intercalating agent is used in the reaction. The labeled primers and/or fluorescent intercalating agents allow quantification of the amounts of amplified products generated in various test reactions.

When nucleic acid amplification is used to detect gene expression, any procedure that amplifies RNA can be used, for example, reverse transcription-polymerase chain reaction (RT-PCR) assays, strand displacement amplification and other amplification procedures. Strand displacement amplification can be used as described in Walker et al (1992) Nucl. Acids Res. 20, 1691-1696. The term “polymerase chain reaction” (“PCR”) refers to the method of K. B. Mullis U.S. Pat. Nos. 4,683,195; 4,683,202; and 4,965,188, hereby incorporated by reference, which describe a method for increasing the concentration of target nucleic acid in a mixture of genomic DNA or other DNA or RNA without cloning or purification.

The steps involved in PCR nucleic acid amplification method are described in more detail below. For ease of discussion, the nucleic acid to be amplified is described as being double-stranded. However, the process is readily adapted to amplify a single-stranded nucleic acid, such as an mRNA from any of the genes listed in Table 1. In the amplification of a single-stranded nucleic acid, the first step involves the synthesis of a complementary strand, for example, by reverse transcription so that two complementary target strands are available for amplification.

When PCR is performed on double-stranded DNA or cDNA generated from one or more of the RNAs expressed from the genes of Table 1, two primers are employed, each primer hybridizing to a different DNA strand at opposite ends of the DNA target. One of skill in the art can readily make and use probes and primers for the genes listed in Table 1, for example, by examining available nucleic acid sequences for these genes that are available in the sequence database maintained by the National Center for Biotechnology Information (see website at http://www.ncbi.nlm.nih.gov/). Examples of some sequences for the genes listed in Table 1 are provided hereinbelow.

The PCR process for amplifying a target nucleic acid consists of introducing a large excess of the two primers to a mixture that may contain the mRNA (or cDNA generated therefrom) from any of the genes listed in Table 1, followed by a precise sequence of thermal cycling in the presence of a nucleic acid polymerase. For PCR amplification, each of the two primers is complementary to a distinct region in one of the two strands of the double stranded target sequence. Primers are selected so that they hybridize just outside the region of interest to be amplified and so that, upon primer extension, one primer will be extended towards the hybridization site of a second primer hybridized on the opposite target strand.

To effect amplification, the nucleic acid (RNA or cDNA) is denatured to open up double-stranded target sites and the temperature is lowered so that the primers anneal to their complementary sequences within the target molecule. Following annealing, the primers are extended with a polymerase. Such primer extension forms a new pair of complementary strands that likely have different ends than the original target. Such complementary strands can hybridize together to form an “amplicon” that can also be a target for amplification. The steps of denaturation, primer annealing and primer extension can be repeated many times. Each round of denaturation, annealing and extension constitutes one “cycle.” There can be numerous cycles, and the amount of amplified DNA produced increases with the number of cycles. Hence, to obtain a high concentration of an amplified target nucleic acid, many cycles are performed.

The following steps are generally employed during nucleic acid amplification with the inhibitors of the invention:

(a) Each target nucleic acid strand is contacted with four different nucleoside triphosphates and one oligonucleotide primer, wherein each primer is selected to be substantially complementary to a portion the nucleic acid strand to be amplified (hmgn3), such that the extension product synthesized from one primer, when it is separated from its complement, can serve as a template for synthesis of the extension product of the other primer. To promote the proper annealing of primer(s) and the nucleic acid strands to be amplified, a selected primer-hybridization temperature is used that allows hybridization of each primer to a complementary nucleic acid strand. The inhibitors of the invention can be added or included in this melting/annealing reaction.

(b) After primer annealing, a nucleic acid polymerase is used for primer extension. The nucleic acid polymerase incorporates the nucleoside triphosphates into a growing nucleic acid strand to form a new strand that is complementary to the template strand hybridized by the primer. In general, this primer extension reaction is performed at a temperature and for a time effective to promote the activity of the nucleic acid enzyme and to synthesize a “full length” complementary nucleic acid strand that extends into and through a complete second primer binding site. However, the temperature is not so high as to separate each extension product from its nucleic acid template strand. The polymerase may be added after the first melting/annealing reaction.

(c) The mixture from step (b) is then heated for a time and at a temperature sufficient to separate the primer extension products from their complementary templates. The temperature chosen is not so high as to irreversibly denature the nucleic acid polymerase present in the mixture.

(d) The mixture from (c) is cooled for a time and at a temperature effective to promote hybridization of a primer to each of the single-stranded molecules produced in step (b).

(e) The mixture from step (d) is maintained at a temperature and for a time sufficient to promote primer extension by the polymerase to produce a “full length” extension product. The temperature used is not so high as to separate each extension product from the complementary strand template. Steps (c)-(e) are repeated until the desired level of amplification is obtained.

In some embodiments, real-time polymerase chain reaction (real time PCR; also called quantitative real time polymerase chain reaction (Q-PCR/qPCR) or kinetic polymerase chain reaction) is employed to quantify the expression of genes. Real-time PCR amplifies and simultaneously quantifies a targeted nucleic acid (e.g., an RNA expressed by one of the genes listed in Table 1). Thus, real-time PCR permits both detection and quantification (as absolute number of copies or relative amount when normalized to DNA input or additional normalizing genes) of a specific nucleic acid (e.g., RNA) in a sample.

Real-time PCR employs many of the same steps as polymerase chain reaction but the amplified DNA product is quantified as it accumulates in the reaction in real time after each amplification cycle. Methods that are often used to quantify the amplified DNA include the use of fluorescent dyes intercalate with double-stranded DNA product, and the use of modified DNA primers that fluoresce when hybridized with a complementary nucleic acid template.

For example, any of the SEQ ID NO:3-118 primers can be used in a real-time PCR assay for evaluating expression levels of the differentially expressed genes. One type of real-time PCR assay that can be employed involves use of SYBRGreen dye. SYBR Green is a dye that binds the minor groove of double stranded DNA. When SYBR Green dye binds to double stranded DNA, the intensity of the fluorescent emissions increases. As more double stranded amplicons are produced, SYBR Green dye signal will increase. During the PCR assay, such a fluorescent signal is directly proportional to the number of amplicons generated.

To detect RNA expression levels, real-time polymerase chain reaction is combined with reverse transcription PCR, where the RNA in a sample is first treated with reverse transcriptase to generate a cDNA that can then be amplified.

Reverse transcription PCR and real-time PCR can be used to quantify relative levels of expression from any of the genes listed in Table 1.

The present invention therefore includes a method for detecting and/or quantifying expression of any of the genes listed in Table 1 (a target nucleic acid) that involves nucleic acid amplification (e.g., reverse transcription PCR and real-time PCR), wherein a sample containing a target nucleic acid that is to be amplified (e.g. a cDNA generated from an RNA sample by reverse transcription) is mixed with 1) primers that are complementary to sequences within the target sequence to be amplified, 2) a thermostable polymerase, and 3) four different nucleoside triphosphates. The normal steps of nucleic acid amplification are then followed—melting, annealing and synthesis—by thermal cycling of the mixture. The primers employed can be linked to a label. In some embodiments, a fluorescent intercalating agent is used in the reaction. The labeled primers and/or fluorescent intercalating agents allow quantification of the amounts of amplified products generated in various test reactions.

Microarrays exploit the preferential binding of complementary nucleic acid sequences. A microarray is typically a glass slide, on to which DNA molecules are attached at fixed locations (spots or features). There may be tens of thousands of spots on an array, each containing a huge number of identical DNA molecules (or fragments of identical molecules), of lengths from twenty to hundreds of nucleotides. The spots on a microarray are either printed on the microarrays by a robot, or synthesized by photo-lithography (similar to computer chip productions) or by ink-jet printing. There are commercially available microarrays, however many labs produce their own microarrays.

Hybridization

Nucleic acid hybridization simply involves contacting a probe and target nucleic acid under conditions where the probe and its complementary target can form stable hybrid duplexes through complementary base pairing (see Lockhart et al., 1999, WO 99/32660, for example). The nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, for example, through detection of an attached detectable label. It is generally recognized that nucleic acids are denatured by increasing the temperature and/or decreasing the salt concentration of the buffer containing the nucleic acids.

Under low stringency conditions (e.g., low temperature and/or high salt) hybrid duplexes (e.g., DNA-DNA, RNA-RNA or RNA-DNA) will form even where the annealed sequences are not perfectly complementary. Thus specificity of hybridization is reduced at lower stringency. Conversely, at higher stringency (e.g., higher temperature or lower salt) successful hybridization occurs with fewer mismatches.

One of skill in the art will appreciate that hybridization conditions may be selected to provide any degree of stringency. Stringency can also be increased by addition of agents such as formamide. Hybridization specificity may be evaluated by comparison of hybridization to the test probes with hybridization to the various controls that can be present (e.g., expression level control, normalization control, mismatch controls, etc.).

In general, there is a tradeoff between hybridization specificity (stringency) and signal intensity. Thus, in some embodiments, the wash is performed at the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity. To better distinguish between the signal and the background, the hybridized sequences (e.g., on a microarray) may be washed at successively higher stringency solutions and read between each wash. Analysis of the data sets thus produced will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest.

As used herein, the terms “hybridize” and “hybridization” refer to the annealing of a complementary sequence to the target nucleic acid, i.e., the ability of two polymers of nucleic acid (polynucleotides) containing complementary sequences to anneal through base pairing. The terms “annealed” and “hybridized” are used interchangeably throughout, and are intended to encompass any specific and reproducible interaction between a complementary sequence and a target nucleic acid, including binding of regions having only partial complementarity. Certain bases not commonly found in natural nucleic acids may be included in the nucleic acids of the present invention and include, for example, inosine and 7-deazaguanine. Those skilled in the art of nucleic acid technology can determine duplex stability empirically considering a number of variables including, for example, the length of the complementary sequence, base composition and sequence of the oligonucleotide, ionic strength and incidence of mismatched base pairs. The stability of a nucleic acid duplex is measured by the melting temperature, or “T_(m)”. The T_(m) of a particular nucleic acid duplex under specified conditions is the temperature at which on average half of the base pairs have disassociated.

The term “stringency” is used in reference to the conditions of temperature, ionic strength, and the presence of other compounds, under which nucleic acid hybridizations are conducted. With “high stringency” conditions, nucleic acid base pairing will occur only between nucleic acid fragments that have a high frequency of complementary base sequences. Thus, conditions of “medium” or “low” stringency are often required when it is desired that nucleic acids which are not completely complementary to one another be hybridized or annealed together. The art knows well that numerous equivalent conditions can be employed to comprise medium or low stringency conditions. The choice of hybridization conditions is generally evident to one skilled in the art and is usually guided by the purpose of the hybridization, the type of hybridization (DNA-DNA or DNA-RNA), and the level of desired relatedness between the sequences (e.g., Sambrook et al. (1989); NUCLEIC ACID HYBRIDIZATION, A PRACTICAL APPROACH, IRL Press, Washington D.C. 1985, for a general discussion of the methods).

The stability of nucleic acid duplexes is known to decrease with an increased number of mismatched bases, and further to be decreased to a greater or lesser degree depending on the relative positions of mismatches in the hybrid duplexes. Thus, the stringency of hybridization can be used to maximize or minimize stability of such duplexes. Hybridization stringency can be altered by: adjusting the temperature of hybridization; adjusting the percentage of helix destabilizing agents, such as formamide, in the hybridization mix; and adjusting the temperature and/or salt concentration of the wash solutions. For filter hybridizations, the final stringency of hybridizations often is determined by the salt concentration and/or temperature used for the post-hybridization washes.

“High stringency conditions” when used in reference to nucleic acid hybridization include conditions equivalent to binding or hybridization at 42° C. in a solution consisting of 5× SSPE (43.8 g/l NaCl, 6.9 g/l NaH₂PO₄ H₂O and 1.85 g/l EDTA, pH adjusted to 7.4 with NaOH), 0.5% SDS, 5×Denhardt's reagent and 100 μg/ml denatured salmon sperm DNA followed by washing in a solution comprising 0.1× SSPE, 1.0% SDS at 42° C. when a probe of about 500 nucleotides in length is employed.

“Medium stringency conditions” when used in reference to nucleic acid hybridization include conditions equivalent to binding or hybridization at 42° C. in a solution consisting of 5× SSPE (43.8 g/l NaCl, 6.9 g/l NaH₂PO₄ H₂O and 1.85 g/l EDTA, pH adjusted to 7.4 with NaOH), 0.5% SDS, 5×Denhardt's reagent and 100 μg/ml denatured salmon sperm DNA followed by washing in a solution comprising 1.0× SSPE, 1.0% SDS at 42° C. when a probe of about 500 nucleotides in length is employed.

“Low stringency conditions” include conditions equivalent to binding or hybridization at 42EC in a solution consisting of 5× SSPE (43.8 g/l NaCl, 6.9 g/l NaH₂PO₄ H₂O and 1.85 g/l EDTA, pH adjusted to 7.4 with NaOH), 0.1% SDS, 5×Denhardt's reagent [50×Denhardt's contains per 500 ml: 5 g Ficoll (Type 400, Pharmacia), 5 g BSA (Fraction V; Sigma)] and 100 g/ml denatured salmon sperm DNA followed by washing in a solution comprising 5× SSPE, 0.1% SDS at 42° C. when a probe of about 500 nucleotides in length is employed.

The term “homology” refers to a degree of sequence identity. There may be partial homology or complete homology (i.e., identity). Homology is often measured using sequence analysis software (e.g., Sequence Analysis Software Package of the Genetics Computer Group. University of Wisconsin Biotechnology Center. 1710 University Avenue. Madison, Wis. 53705). Such software matches similar sequences by assigning degrees of homology to various substitutions, deletions, insertions, and other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine.

It is also understood that these ranges, compositions and conditions for hybridization are mentioned by way of non-limiting examples only, and that the desired stringency for a particular hybridization reaction is often determined empirically by comparison to one or more positive or negative controls. Depending on the application envisioned it is preferred to employ varying conditions of hybridization to achieve varying degrees of selectivity of a nucleic acid towards a target sequence. In a non-limiting example, identification or isolation of a related target nucleic acid that does not hybridize to a nucleic acid under stringent conditions may be achieved by hybridization at low temperature and/or high ionic strength. Such conditions are termed “low stringency” or “low stringency conditions,” and non-limiting examples of low stringency include hybridization performed at about 0.15 M to about 0.9 M NaCl at a temperature range of about 20° C. to about 50° C. Of course, it is within the skill of one in the art to further modify the low or high stringency conditions to suite a particular application.

The hybridization conditions selected also depend on the particular circumstances (depending, for example, on the G+C content, type of target nucleic acid, source of nucleic acid, and size of hybridization probe). Optimization of hybridization conditions for the particular application of interest is well known to those of skill in the art. Representative solid phase hybridization methods are disclosed in U.S. Pat. Nos. 5,843,663, 5,900,481, and 5,919,626, which are incorporated herein by reference in their entireties. Other methods of hybridization that may be used in the practice of the present invention are disclosed in U.S. Pat. Nos. 5,849,481, 5,849,486, and 5,851,772, which are also incorporated herein by reference in their entireties.

Signal Detection

The hybridized nucleic acids are typically detected by detecting one or more labels attached to either the nucleic acids derived from a test sample (e.g., an amplified product) or to a probe that is hybridized to the mRNA or an amplified product of the mRNA. The labels may be incorporated by any of a number of means well known to those of skill in the art (for example, see Affymetrix GeneChip™ Expression Analysis Technical Manual).

DNA arrays and gene chip technology provide a means of rapidly screening a large number of nucleic acid samples for their ability to hybridize to a variety of single stranded DNA probes immobilized on a solid substrate. These techniques involve quantitative methods for analyzing large numbers of genes rapidly and accurately. The technology capitalizes on the complementary binding properties of single stranded DNA to screen nucleic acid samples by hybridization (Pease et al., 1994; Fodor et al., 1991). Basically, a DNA array or gene chip consists of a solid substrate with an attached array of single-stranded DNA molecules. For screening, the chip or array is contacted with a single stranded nucleic acid sample (e.g., cRNA or cDNA), which is allowed to hybridize under stringent conditions. The chip or array is then scanned to determine which probes have hybridized.

Methods for directly synthesizing on or attaching polynucleotide probes to solid substrates are available in the art. See, e.g., U.S. Pat. Nos. 5,837,832 and 5,837,860, both of which are expressly incorporated by reference herein in their entireties. A variety of methods have been utilized to either permanently or removably attach the probes to the substrate. Exemplary methods include: the immobilization of biotinylated nucleic acid molecules to avidin/streptavidin coated supports (Holmstrom, 1993), the direct covalent attachment of short, 5′-phosphorylated primers to chemically modified polystyrene plates (Rasmussen et al., 1991), or the precoating of the polystyrene or glass solid phases with poly-L-Lys or poly L-Lys, Phe, followed by the covalent attachment of either amino- or sulfhydryl-modified oligonucleotides using bifunctional crosslinking reagents (Running et al., 1990; Newton et al., 1993). When immobilized onto a substrate, the probes are stabilized and therefore may be used repeatedly.

In general terms, hybridization is performed on an immobilized nucleic acid target or a probe molecule that is attached to a solid surface such as nitrocellulose, nylon membrane or glass. Numerous other matrix materials may be used, including reinforced nitrocellulose membrane, activated quartz, activated glass, polyvinylidene difluoride (PVDF) membrane, polystyrene substrates, polyacrylamide-based substrate, other polymers such as poly(vinyl chloride), poly(methyl methacrylate), poly(dimethyl siloxane), photopolymers (which contain photoreactive species such as nitrenes, carbenes and ketyl radicals capable of forming covalent links with target molecules).

The Affymetrix GeneChip system may be used for hybridization and evaluation of the probe arrays, where the probes have been selected to hybridize to any combination of the genes listed in Table 1 (or a cRNA or cDNA obtained from an mRNA generated by any of those genes). In some embodiments, the Affymetrix U95A or U133A array is used in conjunction with Microarray Suite 5.0 for data acquisition and preliminary analysis of gene expression patterns and/or levels.

Normalization Controls

Normalization controls are oligonucleotide probes that are complementary to labeled reference oligonucleotides that are added to the nucleic acid sample. The signals obtained from the normalization controls after hybridization provide a control for variations in hybridization conditions, label intensity, “reading” efficiency and other factors that may cause the hybridization signal to vary between arrays. For example, signals read from all other probes in the array can be divided by the signal from the control probes thereby normalizing the measurements.

Virtually any probe may serve as a normalization control. However, it is recognized that hybridization efficiency varies with base composition and probe length. Preferred normalization probes are selected to reflect the average length of the other probes present in the array, however, they can be selected to cover a range of lengths. The normalization control(s) can also be selected to reflect the (average) base composition of the other probes in the array, however in a preferred embodiment, only one or a few normalization probes are used and they are selected such that they hybridize well (i.e. no secondary structure) and do not match any target-specific probes. Normalization probes can be localized at any position in the array or at multiple positions throughout the array to control for spatial variation in hybridization efficiently.

In a some embodiments, a standard probe cocktail supplied by Affymetrix is added to the hybridization to control for hybridization efficiency when using Affymetrix Gene Chip arrays.

Expression Level Controls

Expression level controls are probes that hybridize specifically with constitutively expressed genes in the sample. The expression level controls can be used to evaluate the efficiency of cRNA preparation.

Virtually any constitutively expressed gene provides a suitable target for expression level controls. Typically expression level control probes have sequences complementary to subsequences of constitutively expressed “housekeeping genes.”

In one embodiment, the ratio of the signal obtained for a 3′ expression level control probe and a 5′ expression level control probe that specifically hybridize to a particular housekeeping gene is used as an indicator of the efficiency of cRNA preparation. A ratio of 1-3 indicates an acceptable preparation.

Databases

Any appropriate computer platform may be used to perform the necessary comparisons between sequence information, gene expression information and any other information in a database or provided as an input. For example, a large number of computer workstations and programs are available from a variety of manufacturers, such as those available from Affymetrix.

Statistical Methods

Combining profiles of gene expression over a wide array of transcripts has potentially more classification prediction power than relying on any single gene. The significance of the difference between the levels of gene expression between tissue sample types can be assessed using expression data and any number of statistical tests such as those described in the Examples and by using published methods (e.g., the Significance Analysis of Microarrays (SAM) method, see, Tusher V G, et al., 2001, Proc. Natl. Acad. Sci. USA 98(9):5116-21). SAM identifies genes with statistically significant changes in expression by assimilating a set of gene-specific t-tests. Each gene is assigned a score on the basis of its change in gene expression relative to the standard deviation of repeated measurements for that gene. Genes with scores greater than a threshold are deemed potentially significant. The percentage of such genes identified by chance is the false discovery rate (FDR). To estimate the FDR, nonsense genes are identified by analyzing permutations of the measurements. The threshold can be adjusted to identify smaller or larger sets of genes, and FDRs are calculated for each set.

Kits

The methods described herein can be practiced using a kit. Such kits generally include probes and/or primers for detecting and/or quantifying expression of the differnentially expressed genes described herein, and instructions for performing the detection and/or quantification methods.

Thus, one aspect of the invention is a kit that includes, for example, (a) at least one set of oligonucleotide primers, wherein a first primer in the set contains a sequence complementary to a region in one strand of a nucleic acid sequence template and primes the synthesis of a first extension product, and a second primer contains a sequence complementary to a region in said first extension product and primes the synthesis of a nucleic acid strand complementary to said first extension product, and wherein the template is a differentially expressed gene, or an RNA or DNA copy of the differentially expressed gene; and (b) instructions for using the at least one set of oligonucleotide primers; wherein differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof.

The first primer and/or the second primer provided in the kit can have a covalently attached label. For example, the first primer and/or the second primer can be selected from any of SEQ ID NO:3-118.

Another kit that can be made and/or used for detecting differential expression can include (a) a microarray with covalently attached probes that can hybridize to a differentially expressed gene selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof; and (b) instructions for using the microarray.

Probes useful in the microarray of this kit can hybridize to any of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, or a combination thereof

The kit can include other useful components. For example, the kit can include a container of nucleotides for use as subunits in the synthesis of and amplified product. In some embodiments, the one or more nucleotides provided can have a covalently attached label. The nucleotides provided with the kit can be ribonucleotides or deoxyribonucleotides. Other components provided by the kit include reagents or devices for isolating and/or purifying mRNA, enzymes such as reverse transcriptase, ligase, DNA polymerase (e.g., Taq polymerase), solutions and buffers for performing enzymatic reaction, and/or solutions for performing hybridization. Thus, the kits can include one or more buffers, such as a DNA isolation buffers, an amplification buffer or a hybridization buffer. The kit may also contain compounds and reagents to prepare DNA templates and isolate RNA from a test sample. The kit may also include various labeling reagents and compounds.

The kit of can also include one or more standard or control probes. For example, one or more of the standard or control probes can be a probe or probes for one or more constitutively expressed genes.

In some embodiments the instructions provided with the kit can describe a method for amplifying an mRNA, cRNA or cDNA corresponding to the differentially expressed gene(s). One of skill in the art may choose to utilize the kit for detecting differential expression by hybridization of a first primer and/or a second primer to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene under moderate to highly stringent hybridization conditions. When using the kit with the microarray, one of skill in the art may choose to utilize the kit for detecting differential expression by hybridization of a probe to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene under moderate to highly stringent hybridization conditions. For example, the instructions provided in the kit can inform one of skill in the art to employ hybridization conditions that are moderately to highly stringent hybridization conditions.

The kit can include primers and/or probes for detecting some or all of the differentially expressed genes. For example, the kits can detect and/or quantify expression of a subset of differentially expressed genes such as any one of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 or a combination thereof. The kits can detect and/or quantify expression of other subsets of differentially expressed genes, for example, any one of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, TIAM1 or a combination thereof. Alternatively, for example, the kits can be used to detect another subset of differentially expressed genes such as one or more of the following genes C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 or a combination thereof.

Thus, probes and/or primers for detecting mRNA expression of any of the genes listed in Table 1 may be included in a kit. The kit may further include individual nucleic acids that can be amplified with the nucleic acids of interest. The kit can also include probes and/or primers for detecting particular control nucleic acid sequences. The control nucleic acids included in the kit can be mRNA(s) and/or control cDNA(s). The probes, primers and/or control RNA and/or DNA sequences can be provided on a microarray. Alternatively, the probes, primers and/or control RNA and/or DNA sequences can be provided in separate vials or wells of an assay plate (e.g., a microtiter plate).

Some of the components of the kits may be packaged either in aqueous media or in lyophilized form. When the components of the kit are provided in one and/or more liquid solutions, the liquid solution is an aqueous solution, with a sterile aqueous solution being particularly preferred. However, the components of the kit may also be provided as dried powder(s). When reagents and/or components are provided as a dry powder, the powder can be reconstituted by the addition of a suitable solvent. It is envisioned that the solvent may also be provided in another container or by the user.

The containers for the kits can include at least one vial, test tube, flask, bottle, syringe or other container means, into which a component may be placed, and/or suitably aliquoted. A labeling reagent and label may be included and packaged separately or together. There can be more than one component or container in the kit. For example, the kit can also contain a second, third or other additional container into which the additional components may be separately placed. However, various combinations of components may be included together in a vial. The kits of the present invention can also include a means for containing the nucleic acids, and any other reagent containers in close confinement for commercial sale. Such containers may include injection or blow-molded plastic containers into which the desired vials are retained.

A kit will also include instructions for employing the kit components as well the use of any other reagent not included in the kit. Instructions may include variations that can be implemented.

The following non-limiting examples further illustrate aspects of the invention.

Example 1 Materials and Methods Tumor Samples

Tissue samples were collected at time of surgery, snap-frozen in liquid nitrogen, and stored at −80° C. Representative slides for all tumors were reviewed by two dedicated pathologists. A total of 90 thyroid tumor samples, including 16 papillary thyroid carcinoma (PTC), 22 follicular variants of papillary thyroid carcinoma (FVPTC), 15 hyperplastic nodules, 22 follicular adenomas, and 15 histologically borderline tumors were analyzed in this study. This study was approved by our Institutional Review Board.

Borderline tumors were defined as encapsulated lesions with follicular architecture in which the morphologic features of papillary thyroid carcinoma were qualitatively incomplete and the lesions did not demonstrate evidence of capsular and/or vascular invasion. The incomplete features of papillary thyroid carcinoma were widespread in the lesions that were analyzed in this study and did not represent focal findings in an otherwise benign nodule. An example of such a borderline tumor sample is shown in FIG. 1. In essence, these cases could be classified as well differentiated tumors of uncertain malignant potential (WDT-UMP) as proposed by Williams et al. (Int J Surg Pathol. 8:181-183 (2000)). The officially reported final diagnosis of the 15 borderline tumors, all rendered prior to the onset of this study, was 7 follicular adeonomas and 8 FVPTCs.

RNA Isolation and GeneChip Hybridization

RNA was extracted using RNeasy Mini kit (Qiagen, Valencia, Calif.) from frozen tissue following manufacturer's protocol. RNA purity was confirmed by spectrophotometry. Total RNA was reverse transcribed to complementary DNA (cDNA) according to manufacturer's protocol (NuGEN Ovation RNA Amplification System V2) and then labeled with biotin. cDNA was then hybridized to genechips for microarray analysis, using either GeneChip U95A or U133A (Affymetrix, Santa Clara, Calif.).

Microarray Data Analysis

ArrayAssist 5.2.2 (Stratagene, Inc., La Jolla, Calif.) was used for gene chip analysis. Interchip and intrachip normalization was performed via robust multichip analysis (RMA). After RMA, hybridization signals underwent variance stabilization, log transformation, and baseline transformation. Advanced significance analysis was performed on 50 U95A GeneChips including 10 hyperplastic nodules, 16 follicular adenomas, 13 follicular variants of papillary thyroid carcinomas (FVPTCs), and 11 papillary thyroid carcinomas. This formed the training set. Gene expression of benign tumors was compared to that of malignant tumors. After Benjamini-Hochberg correction for false-discovery, gene probe sets with significant differential expression (2-fold or more with p<0.05) were identified. This probe list was then converted to correspond to probes on the U133A Gene Chips (array comparison software; available from Affymetrix.com). The remaining 40 tumor samples, all analyzed with U133A Gene Chips, formed the test set. The test set was then assessed using unsupervised hierarchical cluster analysis and K-means cluster analysis with both 2- and 3-group cluster algorithms. Genes that were differentially expressed between borderline tumors and classic benign and malignant tumors were further identified with advanced significance analysis.

Detection of BRAF Mutations

All 40 tumors forming the test group were analyzed for v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in which glutamate was substituted for valine at codon 600. One microgram of RNA was reverse-transcribed in a 20 μl reaction and a 1 μl aliquot of cDNA was used for polymerase chain reaction (PCR). The following PCR primers were used:

forward primer, 5′-TGCTTGCTCTGATAGGAAAATG-3′; (SEQ ID NO: 1) and reverse primer,  5′-GACTTTCTAGTAACTCAGCAGC-3′. (SEQ ID NO: 2)

Amplification was carried out for 35 cycles (at 94° C. for 15 seconds, at 60° C. for 1 minute, and at 72° C. for 1 minute). All PCR products were visualized by electrophoresis on a 2% agarose gel and purified using a PCR purification kit (Qiagen Inc). BRAF mutations were detected by direct sequencing of PCR products. All sequencing was performed bidirectionally using the Big Dye Terminator cycle-sequencing kit and the Applied Biosystems Automated 3730 DNA Analyzer (Applied Biosystems, Foster City, Calif.).

Example 2 Accurate Diagnosis of Thyroid Tumors as Benign or Malignant

This Example illustrates that gene expression analysis can be used to identify whether tumors of uncertain malignancy are benign or malignant. Based on their benign clinical behavior, it is proposed that these encapsulated thyroid follicular lesions with partial nuclear features of papillary thyroid carcinoma be called ‘follicular adenomas with nuclear atypia’ and the data indicate that these lesions may not need to be treated as cancers.

Differentiation of Benign and Malignant Tumors

The training set consisted of 50 tumors including 26 unequivocal benign tumors (16 follicular adenoma and 10 hyperplastic nodules) and 24 unequivocal malignancies (11 PTC and 13 FVPTC). A total of 66 probe sets corresponding to 56 genes showed significant differential expression between benign and malignant tumors. Thirty-one genes had up-regulated expression in malignancies compared to benign tumors, and 30 genes were down-regulated (Table 1).

TABLE 1 Genes differentially expressed between benign, borderline, and/or malignant thyroid lesions Gene Fold Gene Name Symbol Change* P Differentially expressed between benign and borderline/malignant lesions Ankyrin 2, neuronal ANK2 −2.70 .0281 Rho GTPase activating protein 6 ARHGAP6 −2.42 .0329 Cadherin 16, kidney-specific cadherin CDH16 −2.28 .0185 Cbp/p300-interacting CITED1 +6.44 .0252 Cbp/p300-interacting CITED2 −2.06 .0261 Cbp/p300-interacting CITED2 −2.76 .0182 Collagen, type IX, alpha 3 COL9A3 −5.87 .0160 Chondroitin beta 1,4 ChGn −3.72 .0111 Dual-specificity phosphatase 4 DUSP4 +3.69 .0206 EGF-containing fibulin-like EFEMP1 −2.60 .0464 engulfment and cell motility 1 ELMO1 −2.60 .0261 Fibroblast growth factor receptor 2 FGFR2 −2.13 .0343 Fibronectin leucine rich transmembrane FLRT1 −2.10 .0252 protein 1 Fibromodulin FMOD −3.09 .0063 Glycine amidinotransferase GATM −2.41 .0482 V-kit Hardy-Zuckerman 4 feline KIT −3.85 .0039 Low-density lipoprotein LRP4 +5.89 .016 Matrilin 2 MATN2 −3.38 .0127 Slit homolog 1 (Drosophila) SLIT1 +3.35 .0258 Spectrin, alpha, nonerythrocytic 1 SPTAN1 +2.66 .0160 Transcription factor CP2-like 1 TFCP2L1 −3.54 .0029 Phosphoinositide-binding protein PIP3-E −3.14 .0343 Pleckstrin and Sec7 domain PSD3 +2.40 .0169 Pleckstrin and Sec7 domain PSD3 +2.55 .0214 Tensin 3 TNS3 −2.41 .0029 Tetraspanin 12 TSPAN12 −2.35 .0047 T-cell lymphoma invasion and TIAM1 +3.91 .0160 metastasis Differentially expressed between malignant and borderline/benign lesions Deiodinase, iodonthyronine, type 1 DIO1 −4.47 .0321 Deltex 4 homolog (Drosophila) DTX4 +3.68 .0111 Uridine diphosphate-N-acetyl-alpha-D- GALNT7 +2.07 .0213 galactosamine High-mobility group AT-hook 2 HMGA2 +3.56 .0204 Insulin-like growth factor binding IGFBP6 +3.18 .0160 protein 6 Met proto-oncogene MET +2.35 .0182 Protein S PROS1 +3.97 .0089 Syndecan 4 SDC4 −3.26 .0049 Serpin peptidase inhibitor, clade A SERPINA1 +5.64 .0252 Serpin peptidase inhibitor, clade A SERPINA1 +4.81 .0233 Solute carrier family 4 SLC4A4 −4.03 .0034 TIMP metallopeptidase inhibitor 1 TIMP1 +2.72 .0446 Uridine phosphorylase 1 UPP1 +2.25 .0127 T-cell lymphoma invasion and TIAM1 +3.91 .0160 metastasis 1 Differentially expressed only between benign and malignant lesions Chromosome 11 open reading frame 17 C11orf17 −2.12 .0239 Calpain 3 CAPN3 +2.00 .0263 Calpain 3 CAPN3 +2.10 .0410 Creatine kinase, brain CKB −2.46 .0189 Cysteine and glycine-rich protein 2 CSRP2 −2.41 .0189 Death-associated protein kinase DAPK2 +2.23 .0322 Dipeptidyl-peptidase 4 DPP4 +2.83 .0127 Dipeptidyl-peptidase 4 DPP4 +2.51 .0117 Homogentisate 1,2-dioxygenase HGD −3.17 .0149 Myosin, heavy chain 10 MYH10 +2.73 .0214 Phosphonoformate immunoassociated PFAAP5 +2.59 .0189 protein 5 Phosphonoformate immunoassociated PFAAP5 +2.28 .0258 protein 5 Placental growth factor PGF −2.22 .0301 Myosin, heavy chain 10 MYH10 +2.73 .0214 PBX/knotted 1 homeobox 2 PKNOX2 −2.31 .0455 Protein kinase, cAMP-dependent PRKACB −2.20 .0241 Glytaminyl-peptide cyclotransferase QPCT +3.43 .0136 RAB27A, member RAS oncogene RAB27A +2.41 .0111 RAB27A, member RAS oncogene RAB27A +2.08 .0063 Retinoid X receptor, gamma RXRG +2.57 .0261 Solute carrier family 25 SLC25A15 −2.75 .0261 GTP indicates guanine triphosphate; Cpb, cyclic adenosine monophosphate response element-binding protein; EGF, epidermal growth factor; Sec7, a guanine-nucleotide-exchange factor (also called ARNO3 and cytohesion 3); AT, adenine and thymine; TIMP, tissue inhibitor of metalloproteinase; cAMP, cyclic adenosine monophosphate. *Fold change is shown relative to benign lesions.

Unsupervised Hierarchical Cluster Analysis

An independent set of 40 test samples was then characterized by observing the expression of genes from the list generated by the training set. The test set included 15 borderline tumors as well as a second group of unequivocal benign (n=11) and malignant (n=14) tumors, including 6 follicular adenomas, 5 hyperplastic nodules, 9 FVPTCs and 5 PTCs. In an unsupervised hierarchical cluster analysis, all benign tumors were distinguished from malignant tumors as expected (FIG. 2).

In addition to these two groups of tumor types, a third intermediate group was identified. This tumor group involved 15 tumors, where the vast majority (10 cases) were histologically borderline tumors. Three FVPTCs and 2 follicular adenomas were also identified in this borderline group of tumor types. Of the 5 remaining borderline tumors, 4 clustered with the benign group and 1 with the malignant group. It is noteworthy that these tumors were the most peripheral nodes in these two groups, indicating an expression profile closer to the intermediate group than other benign and malignant tumors (FIG. 2).

K-Means Cluster Analysis

To help elucidate the differences in gene expression between the three groups of tumors (benign, borderline and malignant), the test set was also subjected to K-means cluster analysis using both 2- and 3-groups. In the 2-group cluster algorithm, tumors were separated into two groups based on their gene expression of the genes of interest. This algorithm distinguished benign and malignant tumors with 93% sensitivity and 82% specificity (FIG. 3). Borderline tumors were divided, with four tumors (27%) grouped with benign tumors while eleven (73%) were grouped with the malignant tumors.

In the 3-group cluster algorithm, tumors were separated into three designated groups based on their expression profile. With this algorithm, malignant tumors primarily formed one group (with 1 borderline tumors), benign tumors formed a second group (with 4 borderline tumors), and a third group was composed of 10 borderline tumors, 2 follicular adenoma, and 3 FVPTC (FIG. 4). These 2 follicular adenomas were previously grouped with malignancies in the 2-group algorithm (FA-3 and FA-4) and one of the three FVPTCs that was grouped with the borderline tumors (FVPTC-3) had previously clustered with the benign tumors in the 2-group algorithm.

Correlation with Final Clinical Diagnosis and Patient Follow-Up

Of 15 borderline tumors included in this study, 7 tumors were officially diagnosed and reported as follicular adenomas (47%) and 8 (53%) as FVPTCs. Upon review of the 2-group K-means cluster analysis of these 15 borderline tumors, a correlation between the reported diagnosis and cluster group was observed in only 6 out of 15 tumors (40%), underscoring the diagnostic dilemmas that pathologists face with these tumors (Table 2).

TABLE 2 Comparison of Final Diagnosis with 2-Group Clustering of Borderline Tumor Samples BOR1-15 Pathologic Cluster Sample Diagnosis Group Concordance BOR 1 FVPTC Benign No BOR 2 FA Benign Yes BOR 3 FA Malignant* No BOR 4 FVPTC Malignant* Yes BOR 5 FA Malignant* No BOR 6 FA Malignant* No BOR 7 FVPTC Malignant* Yes BOR 8 FVPTC Malignant* Yes BOR 9 FA Malignant* No BOR 10 FA Malignant No BOR 11 FVPTC Malignant* Yes BOR 12 FVPTC Malignant* Yes BOR 13 FA Malignant* No BOR 14 FVPTC Benign No BOR 15 FVPTC Benign No

None of the borderline tumors were associated with lymph node metastasis or distant metastasis. Of the 9 patients with histologically borderline tumors who were followed, 6 patients were officially diagnosed with FVPTC, and none developed a recurrence after surgery (mean follow-up 1.7 years; range 2 months to 4.4 years) based on thyroglobulin level, ultrasound studies, or a combination of both methods. Similarly, among the 3 patients with FVPTC in the molecularly intermediate group (FVPTC-1, FVPTC-2, and FVPTC-3), none had lymph node metastasis, extranodal extension, or recurrent disease at follow-up periods of 23 months, 23 months, and 25 months, respectively.

Gene Signature of Borderline Tumors

To identify gene expression profiles that distinguish borderline tumors from either benign or malignant tumors, another advanced significance analysis was performed. Twenty-seven of the 61 genes had significant differential expression between benign and borderline tumors, while 14 of the 61 genes had significant differential expression between malignancies and borderline tumors. Only one of these genes, T-cell lymphoma invasion and metastasis 1 (TIAM1), overlapped between the two comparisons (FIG. 5). Of the 27 genes that distinguished benign from borderline tumors, 8 genes had up-regulated expression in borderline tumors including, CITED-1, and 19 genes were down-regulated including fibroblast growth factor receptor 2 (FGFR-2) (Table 1). Of the 14 genes that distinguished malignant tumors from borderline tumors, 11 genes were up-regulated in malignant tumors, including met proto-oncogene (MET) and the high-mobility group adenine/thymine-hook 2 gene (HMGA2), whereas 2 genes were relatively down-regulated, notably deiodinase-1 (DIO1) (Table 1).

Mutational Analysis of V-Raf Murine Sarcoma Viral Oncogene Homolog B1

BRAF mutational analysis was performed on all tumors in the test set. BRAF mutations were identified in 4 of 14 of the malignant tumors (29%) (Table 3). No borderline tumors or benign tumors had BRAF mutations.

TABLE 3 Presence of BRAF mutation in tumors BRAF mutation Percent PTC (n = 5) 3 60%  FVPTC (n = 9) 1 11%  BOR (n = 15) 0 0% Follicular Adenoma 0 0% (n = 6) Hyperplastic Nodule 0 0% (n = 5) PTC = papillary thyroid carcinoma; FVPTC = follicular variant of papillary thyroid carcinoma; BOR = borderline tumor

Encapsulated follicular lesions with cytologic atypia remain a diagnostic challenge for pathologists. The foregoing experiments employed molecular profiling to identify a third category of thyroid tumors that, based on gene expression data, is likely to be premalignant. This third category of encapsulated follicular tumors with cytologic atypia typically did not fit into previously proposed benign or malignant classification schemes using standard histology, immunohistochemistry, or mutation analysis. The majority of histologically borderline tumors (66.7%) fell into an intermediate group and only a small number share gene expression similarities with benign tumors (26.7%) or malignant tumors (6.7%; Kmeans cluster analysis) (FIG. 4).

Many genes that were expressed differentially between benign tumors and malignant tumors in the training set were classic markers of PTC, including CITED1; dipeptidyl-peptidase 4 (DPP4); FGFR2; and serpin peptidase inhibitor, Glade A (SERPINA1) (see also, Prasad et al., Mod. Pathol. 2005; 18:48-57 (2005); Huang et al., Proc. Natl. Acad. Sci. USA. 98:15044-49 (2001); Jarzab et al., Cancer Res. 65:1587-1597 (2005)).

It is noteworthy that borderline tumors, like malignant tumors, exhibited up-regulated gene expression of CITED 1 and pleckstrin and Sec7 domain 3 (PSD3) and down-regulated gene expression of FGFR2 relative to benign tumors (Table 1). These genes and others listed in Table 1 are potential markers of early tumorigenesis.

In contrast, some genes with expression that was consistently altered in malignant tumors exhibited unchanged expression in the borderline group of tumors. For example, DIO1, a differentiation marker that was consistently lost in PTC, was retained in this borderline group. Conversely, MET, SERPINA1, tissue inhibitor of metalloproteinase 1 (TIMP1), and HMGA2, which are genes that were often activated or over-expressed in PTC, exhibited lower expression in the borderline group of tumors relative to the malignant group. These genes may represent gene expression changes that are involved in the later stages of cancer development. These findings indicate that the histologically borderline tumors are premalignant and still lack the complete phenotype of PTC.

The results of BRAF mutation analysis also were in agreement with other studies (see, Nikiforova et al., J Clin Endocrinol Metab. 2003; 88:5399-5404 (2003)), with mutations identified in 29% of malignancies. To date, BRAF mutations have not been identified in benign lesions or in borderline encapsulated follicular tumors (see, Arora et al., World J. Surg. 32:1237-1246 (2008); Fontaine et al., Oncogene 27:2228-2236 (2008)). Some studies indicate that BRAF mutations are associated with more aggressive tumors (Frasca et al., Endocr Relat Cancer. 15:191-205 (2008); Kebebew et al., Ann Surg. 246:466-471 (2007)) indicating that borderline tumors are more likely to be indolent tumors.

The finding that BRAF mutation is more frequent in classic PTC than in FVPTC also indicates that, for FVPTCs derived from FAs, BRAF either is uninvolved in carcinogenesis or is involved only as a late event. In addition, because of its higher frequency in classic PTC versus FVPTC, BRAF mutational analysis remains of limited usefulness in the diagnostic evaluation of these lesions.

Of the 15 histologically-defined borderline tumors in this study, 10 were clustered in an intermediate group, separate from benign and malignant clusters (FIG. 3). It is noteworthy that not all borderline tumors were separated into this third group: One tumor was clustered with malignant tumors, and 4 tumors were clustered with benign tumors. Conversely, 3 histologically-unequivocal FVPTCs and 2 FAs were identified in the molecularly intermediate group. Given the data provided herein that FAs, borderline tumors, and FVPTCs are stages of a biologic continuum, such an imperfect correlation between the histological classification and molecular data illustrates that accurate diagnosis should not be based on histological analysis alone.

Immunohistochemical markers have been studied in a few well differentiated tumors of uncertain malignant potential (WDT-UMP) with variable results. Papotti et al. (Mod Pathol. 18:541-546 (2005)) studied the expression of galectin-3 and HBME1 in 13 WDT-UMPs and noted some degree of staining with either antibody in 12 of 13 tumors. Immunohistochemical staining for HBME1, Galectin-3, and CK19 (data not shown) in the histologically borderline tumors that were studied as described herein revealed heterogeneous staining patterns. This variability, again, may reflect the biologically borderline nature of these tumors.

Unfortunately, part of the problem with standard diagnostic tools is the need by clinicians to separate tumors into benign or malignant categories. Partially for that reason, the term WDT-UMP proposed by Williams and by Rosai has not been embraced in practice and certainly is not in use at most institutions (Williams et al., Int J Surg Pathol. 8:181-183 (2000); Rosai, Endocr Pathol. 16:279-283 (2005)). Consequently, the majority of borderline tumors, as in the current study, probably are diagnosed as FVPTCs because of pathologists' general preference to err on the side of over-diagnosis for potential legal concerns. Patients are then often subjected, perhaps unnecessarily, to completion thyroidectomies, central neck dissections, and even radioactive iodine therapy. With the current 2-tiered classification (benign and malignant), our 2-Kmeans cluster would place 73% of histologically borderline tumors in the malignant category. However, such classification is somewhat simplistic and does not correlate with the clinical behavior of these tumors.

Several groups have reviewed the outcome of patients with encapsulated PTC, including both classic PTC and FVPTC (Liu et al., Cancer. 107:1255-1264 (2006); Vickery et al., Am J Surg Pathol. 7: 797-807 (1983); Evans et al., Am J Surg Pathol. 11:592-597 (1987). Liu et al. reviewed the outcome data from 42 patients with encapsulated, noninvasive FVPTCs who had a median 10-year follow-up and reported that no patients had recurrences and that none had lymph node metastasis. Vickery identified 10 patients who had encapsulated papillary cancers; in those patients, none had a recurrence, and only 1 patient had developed lymph node metastasis at a median follow-up of 15 years. Evans identified 7 patients who had encapsulated PTC and reported no recurrences or distant metastases at a median follow-up of 13.5 years. The number of studies that specifically have investigated tumors with borderline features is limited, although no tumor recurrences have been reported (Fusco et al., Am J. Pathol. 160:2157-2167 (2002)). Likewise, none of the patients with borderline tumors in the current study had lymph node metastasis, and none of those with clinical follow-up developed recurrent disease or distant metastasis. The data presented here provide evidence that borderline tumors represent a molecularly distinct group of tumors that may not need aggressive treatment.

Example 3 Real Time PCR Methods

This example describes procedures for performing reverse transcription, real-time, quantitative PCR (RT-qPCR).

Total RNA from human cells is isolated by a standard mini-column method, RNAeasy® Mini Kit (Qiagen, Valencia, Calif.). RNA sample quality is evaluated based on electrophoretic integrity of 18S and 28S rRNA bands on a 2100 Bioanalyzer instrument (Agilent, Santa Clara, Calif.) and by standard spectrophotometric absorbance methods at 230, 260 and 280 nm wavelengths on a NanoDrop 1000 (NanoDrop/Thermo Scientific, Wilmington, Del.).

Preparation of cDNA from the RNA samples is carried out using 1.0 μg of total RNA into a standard 20 μl MMLV reverse transcriptase (Promega, Madison, Wis.) reaction according to the manufacturer's instructions using Promega buffers with a combination of 50 μg/ml random hexamers (Integrated DNA Technologies, Coralville, Iowa) and 2.5 ng/μl oligo d(T16) (Integrated DNA Technologies, Coralville, Iowa) to prime the first strand synthesis. Upon completion of the reverse transcription protocol, the cDNA sample is diluted with 91 μl nuclease-free water (˜5 fold) so that 1 μl (˜1/100) is used as the template for individual 25 μl PCR reactions.

SYBR® Green real-time PCR is set up by combining 12.5 μl 2× SYBR® Green PCR Master Mix (Applied Biosystems, Foster City, Calif.) with 1 μl cDNA sample, 1 μl PCR primer mix (10 μM each forward and reverse primers from Tables 4 and 5) and 10 μl nuclease-free water in an appropriate reaction tube or plate. Real-time PCR thermal cycling and detection is performed on either an ABI 7500 (Applied Biosystems, Foster City, Calif.) or Stratagene Mx3005P (Agilent, Santa Clara, Calif.) instrument for 1 cycle of 10 minutes at 95° C., then 40 cycles of 15 seconds at 95° C. and 60 seconds at 60° C., followed by the instrument specific dissociation analysis steps.

Using the instrument's software and a consistent selection of measurement variables, Ct values are determined and relative expression measurements obtained by the ΔΔCt calculation method (Livak, K J, Schmittgen, T D. 2001, Methods 25, 402-408).

Example 4 Primers and Probes for Detection of Differential Expression

This Example describes primers and probes for detecting expression of the differentially expressed genes described herein.

Thus, the sequences of primers with SEQ ID NO:3-118 are shown below in Tables 4 and 5.

Examples of human sequences (SEQ ID NO:119-172) for the differentially expressed genes ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, and UPP1 are shown in Table 6.

TABLE 4 Forward Primers for Nucleic Acid Amplification Of Differentially Expressed Genes Gene Symbol HGNC NIH/NCBI Standard Transcript ID Forward Primer Sequence SEQ ID NO: ANK2 NM_001127493 AATACTGTGAGAAGAAGTG 3 ARHGAP6 NM_001174 GTGCCAAAGGCTGAGGAAATG 4 C11orf17 NM_182901 CTCATGTGGTAGCAGTTGATTC 5 NAUK2 NM_030952 GAAGTCCCGCAAGGAGAATG 6 CAPN3 NM_173090 AGGCTGGCCTCATCCAAAG 7 CDH16 NM_004062 GATCGTGTGTCGCTGCAAC 8 CSGALNACT1 NR_024040 AGGAAACTCATTCAGACTG 9 (ChGn) CITED1 NM_004143 ATGCCAACCAAGAGATGAG 10 CITED2 NM_006079 AATGGGCGAGCACATACAC 11 CITED2 NM_006079 TAATAGGGTGTGGAATGTC 12 CKB NM_001823 CTTCCTAACTTATTGCCTG 13 COL9A3 NM_001853 GGATCTGCGACACCTCAGC 14 CSRP2 NM_001321 GGCCTACAACAAATCCAAAC 15 DAPK2 NM_014326 TAGGACACGCAGGAAAGACCAC 16 D1O1 NM_000792 TTAAACCTGTCCACATTGGTG 17 DPP4 NM_001935 GATAAGAGGGATTAGGGAG 18 DTX4 NM_015177 ATTTCCTTTCTAACACTGTG 19 DUSP4 NM_001394 TCTAGTTACAGTGGATTTAG 20 EFEMP1 NM_001039348 ATCCAGAGTGACAGTGAAC 21 ELMO1 NM_001039459 GACTAAACCTAAATGCCTC 22 FGFR2 NM_000141 ATCCAGCCTCATACCTACATCAG 23 FLRT1 NM_013280 GCTTATTCCATACCATTTC 24 FMOD NM_002023 GGCTCTTCTCCCTCTCCCAG 25 GALNT7 NM_017423 GTTGGTAATATCACTATGC 26 GATM NM_001482 GTAATTGGATTTCGCTATC 27 HGD NM_000187 GATGAGAACTACCACAAGTGCTG 28 HMGA2 NM_003483 TGTACTTTGAATCGCTTGCTTGTTG 29 IGFBP6 NM_002178 TGCAGCAACTCCAGACTGAG 30 KIT NM_001093772 TTGTGTGTTGTCTTGAAAG 31 LRP4 NM_002334 GAAGCGATTCTCCCATGCTC 32 MATN2 NM_030583 TACGATAAAGTTTGCACAG 33 MET NM_001127500 GAAAGAACTGTCTCTACCAG 34 MYH10 NM_005964 ACTACAAGCAGAGACTGAG 35 PFAAP5 U50535 CAAGGCAGGCAGATTGTTTG 36 PFAAP5 CR601845 TTAGCGGACATGGGTCAATTTC 37 PGF NM_002632 GCTTGTACTGGGACATTGTTC 38 IPCEF1 NM_001130700 GATCCAGGACATCTATCAG 39 (PIP3-E) PKNOX2 NM_022062 AGCACGGACACACTGGCAC 40 PRKACB NM_002731 GTGAAAGCACCTTGTAAAC 41 PROS1 NM_000313 AGTAAGGAGGTAAGATTGC 42 PSD3 NM_206909 GGTAGTGTCTAAGTGGTATG 43 PSD3 NM_206909 TGACTTTCAACTAACCTTG 44 QPCT NM_012413 GATATTGTGTCCTAAATTGC 45 RAB27A NM_183236 TGCCAATGGGACAAACATAAG 46 RAB27A NM_183236 GATGCCTGTTTGCTATTTGGTGGAAG 47 RXRG NM_006917 ATTGTACTCTTTAACCCAG 48 SDC4 NM_002999 CTTCCTCAGTTGCACTAACCAC 49 SERPINA1 NM_000295 TCTGCCAGCTTACATTTACCCAAAC 50 SLC25A15 NM_014252 GTGACCGCTCTTGCTCTTG 51 SLC4A4 NM_003759 AAGAGTGAATAGTTGCCTC 52 SLIT1 NM_003061 CTAGAGGCTGGTTTAGAAC 53 SPTAN1 NM_003127 AGTTTGTAGCCAATGTGGAAG 54 TFCP2L1 NM_014553 TGATTTCCTGTTATGAGTC 55 TIAM1 NM_003253 TTCCATATCATCTCCGGTTCG 56 TIMP1 NM_003254 GACTCTTGCACATCACTAC 57 TNS3 NM_022748 TGTGCCCAACGCATGTTATAG 58 TSPAN12 NM_012338 AGAAAGGACTTGTATGCTG 59 UPP1 NM_181597 GTGTGTGTCACCCTCCTGAAC 60

TABLE 5 Reverse Primers for Nucleic Acid Amplification of Differentially Expressed Genes Gene Symbol HGNC NIH/NCBI Standard Transcript ID Reverse Primer Sequence SEQ ID NO: 1 ANK2 NM_001127493 TTGCAGCTATGTATTGTTAG 61 ARHGAP6 NM_001174 GATGGCGATACGCTTCAGTA 62 Cl1orf17 NM_182901 AAGGTGATGTGATGGCAGTG 63 NAUK2 NM_030952 TTGGCAGCTTGAGGTTGCTC 64 CAPN3 NM_173090 CTTGATCGGTCATGCCTAGCC 65 CDH16 NM_004062 GTAGGCACCCTGGTAGCAA 66 CSGALNACT1 NR_024040 AAGAGATTGTTTGGTTCAC 67 (ChGn) CITED1 NM_004143 CTCGGGATCTCCAATAGGCTCTC 68 CITED2 NM_006079 GTGCCCTCCGTTCACAGTC 69 C1TED2 NM_006079 AGC′TTTCAACACAGTAGTATC 70 CKB NM_001823 ATAAACTCTACCAAGGGTG 71 COL9A3 NM_001853 CGTGAGGAAGCAAGTGACA 72 CSRP2 NM_001321 GAGAAGATAATTGGAGCTGGAA 73 DAPK2 NM_014326 CAATCTTAGACTCTGGCCTCAA 74 D1O1 NM_000792 GCTCTCTGTACCCTGAAATCTTC 75 DPP4 NM_001935 GTTTGAATAGTCTTTCTCAG 76 DTX4 NM_015177 GTCAAGGTAGTAGATGCAC 77 DUSP4 NM_001394 GCTACCTTGCACATATCTAC 78 EFEMP1 NM_001039348 GATACATCAAAGTAAAGCAG 79 ELMO1 NM_001039459 ATGATGTAAACTTGGATGTC 80 FGFR2 NM_000141 CAATAGCCGTGCAAGATGAATG 81 FLRT1 NM_013280 ATCGACTACATGATTGTTC 82 FMOD NM_002023 GTATGAGACCTACGAGCCTTACC 83 GALNT7 NM_017423 ACCCAGAATTAAGATATACG 84 GATM NM_001482 CTTAGATGACCAAAGATGC 85 HGD NM_000187 CTTTCTGGTAGTATTGGAGGAGG 86 HMGA2 NM_003483 CAGAGGCTGTTATGTTTATTGTG 87 IGFBP6 NM_002178 CATCGAGGCTTCTACCGGAA 88 KIT NM_001093772 AGAGCATAGAACTCCAGTG 89 LRP4 NM_002334 CACTGGAGAGATTGGACTTTC 90 MATN2 NM_030583 TATATCAAGGTAAAGTCCAG 91 MET NM_001127500 CAAGTGTGTAGTCCTGTTG 92 MYH10 NM_005964 GGTTTCTTTCTTCTTCTTC 93 PFAAP5 U50535 AATGGCACGATCATGGGTC 94 PFAAP5 CR601845 AAGTGTAGCCCAGGTTAAGAAC 95 PGF NM_002632 GAGAAACAGCTCAGCCAGTGG 96 1PCEF1 NM_001130700 AAGGTGATTTCTTGAGTTC 97 (PIP3-E) PKNOX2 NM_022062 CTGATGTATCCACCAAACCAGTAC 98 PRKACB NM_002731 CAGTAGTGCATAGGAAATTC 99 PROS1 NM_000313 CAGTGAAACATCTGATACAC 100 PSD3 NM_206909 ATAGTCATGGACATTTACAG 101 PSD3 NM_206909 AAGTTACTAAGACTGCACAG 102 QPCT NM_012413 CTATCGTTGAATGAATGAAC 103 RAB27A NM_183236 CTGAAGGAGTGGTGCGATCAA 104 RAB27A NM_183236 GAAGACACTTTGGCAATGCAGCGG 105 RXRG NM_006917 GATACTTCTGCTTGGTGTAG 106 SDC4 NM_002999 GACGACCCTTGTCTCCCTG 107 SERPINA1 NM_000295 GCATCACTAAGGTCTTCAGCA 108 SLC25A15 NM_014252 GTGGTCAGTAGCCTTATGCACCT 109 SLC4A4 NM_003759 ATCATTTCTCTCTCCAAAG 110 SLIT1 NM_003061 GGAAGACAACAGACAATATC 111 SPTAN1 NM_003127 GATTATGGCGACACTCTTGCC 112 TFCP2L1 NM_014553 TACAGTGATGACAGACAGC 113 TIAM1 NM_003253 CTTGGAGAGGGTGCCATTGTC 114 TIMP1 NM_003254 GATAAACAGGGAAACACTG 115 TNS3 NM_022748 CTTGTAACGTCTTCTCTGCCT 116 TSPAN12 NM_012338 TATTGACTTGGAGACTATTG 117 UPP1 NM_181597 GAAGAAACTGAGCAAGGCC 118

Sequences of the coding regions of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIOL, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, and/or UPP1 can be used to develop probes and primers for detecting differential expression of these genes. Such sequences are available in the database maintained by the National Center for Biotechnology Information (NCBI). See website at ncbi.nlm.nih.gov. A few examples of such sequences are provided below.

One example of a nucleic acid sequence for human ANK2 is available as NCBI accession number NM_(—)001148 (gi: 188595661). This sequence is recited below for easy reference as SEQ ID NO:119.

1 ctcctcctcc tgctttcctc cagtaagtgc atacccgcta gtggtctgta caggcggcac 61 ggtttgatgg cagagatatt ttctttccaa actgttcaaa atgatgaacg aagatgcagc 121 tcagaaaagc gacagtggag agaagttcaa cggcagtagt cagaggagaa aaagacccaa 181 gaagtctgac agcaatgcaa gcttcctccg tgctgccaga gcaggcaacc tggacaaagt 241 tgtggaatat ctgaaggggg gcatagacat caatacctgc aatcagaatg gactcaacgc 301 tctccatctg gctgccaagg aaggccacgt ggggctggtg caggagctgc tgggaagagg 361 gtcctctgtg gattctgcca ctaagaaggg aaataccgct cttcacattg catctttggc 421 tggacaagca gaagttgtca aagttcttgt taaggaagga gccaatatta atgcacagtc 481 tcagaatggc tttactcctt tatacatggc tgcccaagag aatcacattg atgttgtaaa 541 atatttgctg gaaaatggag ctaatcagag cactgctaca gaggatggct ttactcctct 601 agctgtggca ctccagcaag gacacaacca ggcggtggcc atcctcttgg agaatgacac 661 caaagggaaa gtgaggctgc cagctctgca tattgccgct aggaaagacg acaccaaatc 721 tgccgcactt ctgcttcaga atgaccacaa tgctgacgta caatccaaga tgatggtgaa 781 taggacaact gagagtggtt ttaccccttt gcacatagct gcacattacg gaaatgtcaa 841 cgtggcaact cttcttctaa accggggagc tgctgtggac ttcacagcca ggaatggaat 901 cactcctctg catgtggctt ccaaaagagg aaatacaaac atggtgaagc tcttactgga 961 tcgaggcggt cagatcgatg ccaaaactag ggatgggttg acaccacttc actgtgctgc 1021 acgaagtggg catgaccaag tggtggaact tctgttggaa cggggtgccc ccttgctggc 1081 aaggactaag aatgggctgt ctccactaca catggctgcc cagggagacc acgtggaatg 1141 tgtgaagcac ctgttacagc acaaggcacc tgttgatgat gtcaccctag actacctgac 1201 agccctccac gttgctgcgc actgtggcca ctaccgtgta accaaactcc ttttagacaa 1261 gagagccaat ccgaacgcca gagccctgaa tggttttact ccactgcaca ttgcctgcaa 1321 gaaaaaccgc atcaaagtca tggaactgct ggtgaaatat ggggcttcaa tccaagctat 1381 aacagagtct ggcctcacac caatacatgt ggctgccttc atgggccact tgaacattgt 1441 cctccttctg ctgcagaacg gagcctctcc agatgtcact aacattcgtg gtgagacggc 1501 actacacatg gcagcccgag ccgggcaggt ggaagtggtc cgatgcctcc tgagaaatgg 1561 tgcccttgtt gatgccagag ccagggagga acagacacct ttacatattg cctcccgcct 1621 gggtaagaca gaaattgtcc agctgcttct acaacatatg gctcatccag atgcggccac 1681 tacaaatggg tacacaccac tgcacatctc tgcccgggag ggccaggtgg atgtggcatc 1741 agtcctattg gaagcaggag cagcccactc cttagctacc aagaagggtt ttactcccct 1801 gcatgtagca gccaagtatg gaagcctgga tgtggcaaaa cttctcttgc aacgccgtgc 1861 tgccgcagat tctgcaggga agaacggcct taccccgctc catgttgctg ctcattatga 1921 caaccagaag gtggcgctgc tgttactgga gaagggtgct tcccctcatg ccactgccaa 1981 gaatggctat actccgttac atattgctgc caagaagaat caaatgcaga tagcttccac 2041 actcctgaac tatggagcag agacaaacat tgtgacaaag caaggagtaa ctccactcca 2101 tctggcctcg caggaggggc acacagatat ggttaccttg cttctggata agggagccaa 2161 tatccacatg tcaactaaga gtggactcac atccttacac cttgcagccc aggaagataa 2221 agtgaatgtt gctgatattc tcaccaagca tggagctgat caggatgctc atacaaagct 2281 tggttacaca cctttaattg tggcctgtca ctatggaaat gtgaaaatgg tcaactttct 2341 tctgaagcag ggagcaaatg ttaacgcaaa aaccaagaac ggctacacgc ctttgcacca 2401 ggccgctcag cagggtcaca cgcacatcat caacgtcctg ctccagcatg gggccaagcc 2461 caacgccacc actgcgaatg gcaacactgc cttggcgatt gctaagcgtc tgggctacat 2521 ctccgtggtc gacaccctga aggttgtgac tgaggaggtc accaccacca ccacaactat 2581 tacagaaaaa cacaaactaa atgtacctga gacgatgact gaggttcttg atgtttctga 2641 tgaagagggt gatgacacaa tgactggtga tgggggagaa taccttaggc ctgaggacct 2701 aaaagaactg ggtgatgact cactacccag cagtcagttc ctggatggta tgaattacct 2761 gcgatacagc ttggagggag gacgatctga cagccttcga tccttcagtt ccgacaggtc 2821 tcacactctg agccatgcct cctacctgag ggacagtgcc gtgatggatg actcagttgt 2881 gattcccagt caccaggtgt caactctagc caaggaggca gaaaggaatt cttatcgcct 2941 aagctggggc actgagaact tagacaacgt ggctctttct tctagtccta ttcattcagg 3001 tttcctggtt agttttatgg tggatgcccg aggtggtgct atgcgaggat gcagacacaa 3061 tgggctccga atcattattc cacctcggaa atgtactgct ccaacgcgag tcacctgccg 3121 actggtcaag cgccacagac tggcaacaat gcctccaatg gtggaaggag aaggcctggc 3181 cagtcgcctg atcgaagttg gaccttctgg tgctcagttc cttggtaaac ttcacctgcc 3241 aacggctcct cccccactta atgagggaga aagtttggtc agccgcattc ttcagctggg 3301 gcctcctgga accaaattcc ttgggcctgt gatcgtggag atccctcact ttgcggccct 3361 tcgaggaaag gaaagggaac tggtggtcct gcgcagtgag aatggggaca gctggaaaga 3421 gcatttctgt gactacactg aagatgaatt gaatgaaatt cttaacggca tggatgaagt 3481 actggatagc ccagaagacc tagaaaagaa acgaatctgc cgcatcatca cccgagactt 3541 cccacagtac tttgcagtgg tgtctcgtat caaacaggac agcaatctga ttggcccaga 3601 aggaggtgta ctgagcagca cagtggtgcc ccaggtgcag gccgtcttcc cagagggggc 3661 actcaccaag cggatccgcg taggcctgca ggctcaacct atgcacagtg agctggttaa 3721 gaagatccta ggcaacaaag ctaccttcag ccctatagtc actttggaac ctagaagaag 3781 aaaattccac aaaccaatta ccatgaccat tcctgtcccc aaagcttcaa gtgatgtcat 3841 gttgaatggt tttgggggag atgcaccaac cttaagatta ctatgcagca taacaggtgg 3901 aaccacccct gcccagtggg aagatattac aggaactacg ccattaacat ttgtcaatga 3961 atgtgtttcc tttacaacaa acgtgtctgc caccttctgg ctgatagatt gtcgacagat 4021 ccaggaatcc gttacttttg catcacaagt atacagagaa attatctgcg taccttatat 4081 ggccaaattt gtagtgtttg ccaaatcaca tgaccccatt gaagccaggt tgaggtgttt 4141 ctgcatgact gatgataaag tggataagac ccttgaacaa caagaaaatt ttgctgaggt 4201 ggccagaagc agggatgtgg aggtgttaga aggaaaaccc atctacgttg attgtttcgg 4261 caacttggta ccattaacta aaagtggcca gcatcatata ttcagttttt ttgccttcaa 4321 agaaaataga cttcctctat ttgtcaaggt acgcgatacg actcaggaac cttgcggacg 4381 actatcattt atgaaggagc caaaatccac gagaggcctg gtgcatcaag ctatttgcaa 4441 cttaaacatc actttgccga tttatacaaa ggaatcagag tcagatcaag aacaggagga 4501 agagatcgat atgacatcag aaaaaaatga tgagacagaa tctacagaaa catctgtcct 4561 gaaaagtcac ctggttaatg aagttcctgt cctagcaagt ccggacttgc tctctgaagt 4621 ttctgagatg aaacaagatt tgatcaaaat gaccgccatc ttgaccacag atgtgtctga 4681 taaggcaggt tctattaaag tgaaggagct ggtgaaggct gctgaggaag agccaggaga 4741 gccttttgaa atcgttgaaa gagttaaaga ggacttagag aaagtgaatg aaatcctgag 4801 aagtggaacc tgcacaagag atgaaagcag tgtgcagagc tctcggtctg agagaggatt 4861 agttgaagag gaatgggtta ttgtcagtga tgaggaaata gaagaggcta ggcaaaaagc 4921 acctttagaa atcactgaat atccatgtgt agaagttaga atagataaag agatcaaagg 4981 aaaagtagag aaagactcaa ctgggctagt gaactacctt actgatgatc tgaatacctg 5041 tgtgcctctt cccaaagagc agctgcagac agttcaagat aaggcaggga agaaatgtga 5101 ggctctggct gttggcagga gctctgaaaa ggaagggaaa gacatacccc cagatgagac 5161 acagagtaca cagaaacagc acaaaccaag cttgggaata aagaagccag taagaaggaa 5221 attaaaagaa aagcagaaac aaaaagagga aggtttacaa gctagtgcag agaaagctga 5281 acttaaaaaa ggtagttcag aagagtcatt aggtgaagac ccaggtttag cccctgaacc 5341 ccttcccact gtcaaggcca catctccttt gatagaagaa actcccattg gttccataaa 5401 ggacaaagta aaggcccttc agaagcgagt ggaagatgaa cagaaaggtc gaagcaagtt 5461 gcccatcaga gtcaaaggca aggaggacgt gccaaaaaag accacccaca ggccacatcc 5521 agctgcgtca ccctctctga agtcagagag acatgcgcca gggtctccct cccctaaaac 5581 agaaagacac tctactcttt cctcttccgc aaaaactgaa aggcaccctc cagtatcacc 5641 atcaagtaaa actgagaaac actcacctgt gtcaccctct gcaaaaacgg aaagacattc 5701 acctgcgtca tcatcgagta aaactgagaa acactcacct gtatcaccct cgacaaaaac 5761 tgaaaggcac tctcctgtgt catctacaaa aacagaaaga cacccacctg tttcgccttc 5821 aggcaaaaca gacaaacgtc cacctgtatc gccctccggg aggacagaaa aacacccgcc 5881 agtatcgcct gggagaacag aaaaacgctt gcctgtttca ccctccggaa gaacggacaa 5941 gcaccaacct gtatcaacag ctgggaaaac tgagaagcac ctgcctgtgt caccttctgg 6001 caaaacagaa aagcaaccac ctgtatcccc cacttcaaaa acagagagga ttgaggaaac 6061 catgtctgtt cgggagctga tgaaggcttt ccagtcaggt caggaccctt ctaaacataa 6121 aactggactc tttgagcaca aatcagcaaa acaaaagcag ccacaagaga aaggtaaagt 6181 tcgggtagaa aaagaaaagg ggccgatact aacccagaga gaagctcaga aaacagagaa 6241 tcagacaatc aaacgaggcc agagactccc ggtaacgggc acagcagaat ccaaaagagg 6301 agttcgtgtt tcctccatag gagttaagaa agaagatgca gctggaggaa aggagaaagt 6361 tctcagccac aaaatacctg aacctgttca gtcagtgcct gaagaagaaa gccacagaga 6421 gagcgaagtg cccaaagaaa agatggctga tgagcaggga gacatggatc tacagatcag 6481 cccagatagg aaaacctcca ctgacttctc tgaggtcatt aagcaagagt tggaagacaa 6541 tgacaaatac caacaattcc gcctgagtga ggagacagaa aaggcacagc ttcacttaga 6601 ccaagtactc actagtcctt tcaacacaac atttccactc gactacatga aagatgagtt 6661 ccttccagct ctgtctttac aaagcggtgc tttagatggc agttctgaaa gcctaaagaa 6721 tgagggggta gccggctctc cgtgtggcag cctgatggag gggacccctc agattagttc 6781 agaagaaagc tataagcatg aaggcctagc agagacccct gagacgagcc cagaaagcct 6841 ttctttctca ccaaagaaaa gtgaggagca aactggggaa acaaaggaaa gcaccaagac 6901 agaaaccacc acagaaattc gttcagaaaa agagcatccc acgaccaaag acattactgg 6961 tggctctgaa gagcgaggtg ccacagtcac tgaggactca gagacctcta ctgagagttt 7021 tcagaaagag gccactctag gctctcccaa agacacaagc cctaaaagac aagatgattg 7081 cacaggcagc tgtagtgtag cattagctaa agagacacct acaggactga ctgaggaggc 7141 agcctgtgat gaaggtcaac gtacctttgg tagttcagcc cacaagacac aaactgatag 7201 tgaggttcaa gaatccacag ccacctcaga cgagacaaag gccttgccgc tgcctgaggc 7261 ttctgtaaag acagatacag gaactgaatc aaaacctcag ggagtcatta gaagtcccca 7321 agggttagaa cttgcactcc ctagccgaga tagcgaagtc ctcagcgctg tggctgatga 7381 ctcattagca gtgagccaca aagactctct ggaagccagc cctgtgctag aagataactc 7441 ttcacacaaa acccctgatt ctctggagcc aagtcctctg aaagaatccc cttgccgtga 7501 ctctctggaa agcagccctg ttgaaccaaa gatgaaggct ggaatttttc caagtcactt 7561 tcctcttcct gcagctgttg ccaaaacaga actcttgacg gaagtggcct ctgtgcggtc 7621 ccggctactc cgagaccctg atggcagtgc tgaggatgac agtcttgagc agacatcgct 7681 catggagagc tcagggaaga gccccctttc tcctgacacc cccagctctg aagaagtcag 7741 ctatgaggtt acacccaaaa ccacagatgt aagtacacca aaaccagctg tgattcatga 7801 atgtgcagag gaggatgatt cagaaaacgg ggagaaaaag aggttcacac ctgaagagga 7861 gatgtttaaa atggtaacca aaatcaaaat gtttgatgaa cttgaacaag aagcaaagca 7921 gaaaagggac tacaaaaaag aacccaaaca agaagaatct tcttcatctt ctgacccaga 7981 tgctgactgt tcagtagatg tggatgaacc aaaacataca ggcagtgggg aggatgaaag 8041 tggtgtccct gtgttagtaa cttcggagag caggaaggtg tcttcctcct cagaaagtga 8101 acctgagttg gcacagctta aaaaaggtgc tgactcaggc cttttaccag aaccagtgat 8161 tcgagtacaa cctccttctc cacttccatc aagcatggac tccaattcca gtccagaaga 8221 agtacaattc cagcctgtcg tttccaaaca atatactttc aagatgaatg aagatactca 8281 ggaagagcca ggcaaatcag aagaagaaaa agattctgaa tcccatttag ctgaagaccg 8341 tcatgctgtt tccactgagg ctgaagacag gtcttatgat aagctaaaca gagacactga 8401 tcagccaaaa atctgtgatg gccatggatg tgaggccatg agtcctagca gctcagctgc 8461 tcctgtctct tcaggtctac agagtccgac tggtgatgat gttgatgaac agccagtcat 8521 ctataaagaa tcattagctc tccaaggcac tcatgaaaaa gacacagagg gagaagagct 8581 tgatgtttct agagcagaat ctccacaagc agattgcccc agtgaaagct tttcatcttc 8641 atcctctttg cctcattgtt tggtatctga aggaaaagaa ttagatgaag acatatctgc 8701 cacatcttct attcaaaaaa cagaggtcac aaaaactgat gaaacatttg agaacttacc 8761 aaaggactgc ccctctcaag actcatccat tactactcaa acagatagat tttccatgga 8821 tgttcccgtg tctgacctag ctgagaatga tgaaatctat gatccacaaa tcactagccc 8881 ttatgaaaat gtcccttccc aatctttttt ctctagtgaa gaaagcaaaa cccaaacaga 8941 tgcaaatcac accacaagtt ttcactcttc tgaagtgtat tctgttacca tcacatcccc 9001 tgttgaagac gttgtagtgg caagctcctc tagtggaact gttttaagca aagaatctaa 9061 ttttgagggc caggacataa aaatggaatc ccaacaggaa agtaccttgt gggaaatgca 9121 atcagacagt gtctcttcat ctttcgagcc tactatgtcc gctacaacaa cagttgttgg 9181 tgaacaaata agcaaagtca tcatcacaaa aactgatgtg gattctgatt cttggagtga 9241 aattcgggaa gacgatgaag cctttgaggc tcgtgtgaaa gaggaagaac aaaagatatt 9301 tggtttgatg gtagacagac aatcacaggg taccacccct gacaccactc ctgctaggac 9361 cccaactgaa gaggggaccc caacaagtga gcaaaaccca tttctgtttc aggaaggaaa 9421 attgtttgaa atgacccgaa gtggtgccat tgatatgacc aaaaggtcct atgcagatga 9481 aagttttcac tttttccaaa ttggtcaaga atccagggaa gagactctct ctgaagatgt 9541 gaaagaaggg gctactgggg ctgatcccct accgctggag acatcagctg aatcactagc 9601 actttcagaa tcaaaagaaa cagtggatga tgaggcagac ttacttccag atgacgtgag 9661 tgaggaagta gaggaaatac ctgcttcgga tgctcaactt aactcccaaa tggggatttc 9721 agcctccact gaaacaccta caaaagaagc tgttagtgta gggaccaagg acctccccac 9781 cgtgcaaacg ggtgatatac ctcctctctc tggtgtaaag cagatatcct gccccgactc 9841 ttctgaacca gctgtacaag tccagttaga tttttccaca ctcaccaggt ctgtttattc 9901 agataggggt gatgattctc ccgattcttc cccagaagaa cagaaatcag taatcgagat 9961 tcctactgca cccatggaga atgtgccttt tactgaaagc aaatccaaaa ttcctgtaag 10021 gactatgccc acttccaccc cagcacctcc atctgcagag tatgagagtt cagtttctga 10081 agattttcta tccagtgtag atgaggaaaa taaggcggat gaagcaaaac caaagtccaa 10141 actccctgtc aaagtacccc tccaaagagt tgaacagcag ctctcagatc tagacacctc 10201 tgtccagaag acagtggctc ctcagggaca ggacatggca agcatcgcac cagataatag 10261 aagcaaatct gaatctgatg ctagttcttt ggattcaaag accaaatgcc cagtaaaaac 10321 ccgaagttac actgagacag aaacagagag cagagagagg gccgaggaac ttgagttaga 10381 atcagaagaa ggggccacaa gaccaaagat acttacatcc cgattgccag ttaagagcag 10441 aagcactaca tcttcctgca gggggggcac gagccccaca aaagaaagta aggagcattt 10501 ctttgacctt tacagaaatt ccatagaatt ctttgaggag attagtgatg aggcttccaa 10561 attagtggat aggctgacac agtcagagag ggagcaggaa atagtttcag acgatgaaag 10621 tagtagtgcc ctggaagtat cagtaattga aaatctgcca cctgttgaga ccgagcactc 10681 agttcctgag gacatctttg acacaaggcc catttgggat gagtctattg agactctgat 10741 tgaacgcatc cctgatgaaa atggccatga ccatgctgaa gatccacagg atgagcagga 10801 acggatcgag gaaaggctgg cttatattgc tgatcacctt ggcttcagct ggacagaatt 10861 agcaagagaa ctggatttca ctgaggagca aattcatcaa attcgaattg aaaatcccaa 10921 ctctcttcaa gaccagagtc atgcactgtt gaagtactgg ctagagaggg atgggaaaca 10981 tgctacagat accaacctcg ttgaatgtct caccaagatc aaccgaatgg atattgttca 11041 tctcatggag accaacacag aacctctcca ggagcgcatc agtcatagtt atgcagaaat 11101 tgaacagacc attacactgg atcatagtga agggttctcg gtacttcaag aggagttatg 11161 cactgcacag cacaagcaga aagaggagca agctgtttct aaagaaagtg agacctgcga 11221 tcaccctcct atcgtctcag aggaagacat ttctgttggt tattccactt ttcaggatgg 11281 cgtccccaaa actgaggggg acagctcagc aacagcactc tttccccaaa ctcacaagga 11341 gcaagttcaa caggatttct cagggaaaat gcaagacctg cctgaagagt catctctgga 11401 atatcagcag gaatattttg tgacaactcc aggaacagaa acatcagaga ctcagaaggc 11461 tatgatagta cccagctctc ccagcaagac acctgaggaa gttagcaccc ctgcagagga 11521 ggagaagctg tacctccaga ccccaacatc cagcgagcgg ggaggctctc ccatcataca 11581 agaacccgaa gagccctcag agcacagaga ggagagctct ccgcggaaaa ccagcctcgt 11641 aatagtggag tctgccgata accagcctga gacctgtgaa agactcgatg aagatgcagc 11701 ttttgaaaag ggagacgata tgcctgaaat acccccagaa acagtcacag aagaagaata 11761 cattgatgag catggacaca ccgtggtaaa gaaggttact aggaaaatca ttaggcggta 11821 tgtatcctct gaaggcacag agaaagaaga gattatggtg cagggaatgc cacaggaacc 11881 tgtcaacatc gaggaagggg atggctattc caaagttata aagcgtgttg tattgaagag 11941 tgacaccgag cagtcagagg acaacaatga gtaaagccat cacacagaag agggctgtgg 12001 tgaaggacca gcatggaaaa cgcattgact tggagcacct ggaggatgta ccagaagcac 12061 tagaccagga cgacctccag cgcgatctcc agcagctcct tcggcatttc tgcaaggagg 12121 acttgaagca agaggccaag tgaggggctg cccagttctc acaccagaaa ccacacattc 12181 actcaatatg cagcttcctg tttcagtagg ggagtgacct aactggccta attaatggga 12241 taccccgaca tttccactgt tagcaaatat acggcatttt gctttagttt tcccccatcc 12301 tctttaacta taaagctaat ttgtgaccaa agatggcatc cttcatactg gatgctgtat 12361 ccaatacttt gttgtgtctg tgctaacctg ggaactggcc acctccattg ttctttgctt 12421 ctgcacaaga tccatgaaaa tccattgatc agaagaactt cacctgcaga cctcttcaag 12481 tgacactatg taggaatcct tccaaggaat atctatgtac aatgtatata gctgaaatgc 12541 tcagatgaac aacatattaa aattaaaacc actgcctatt gtaactacac tgggcatcag 12601 aataaaaggc ctctagaaat tgctgaacaa tggttaatta agatattgct aacacaatcg 12661 agtgataata cagttttact gcaaaagaag cacttcaaac ctattatgtc cttagaactt 12721 ccagagtagc cactgctccc agttaaaggt gggtcagtag ccttgcagaa ctgtcctgag 12781 aagttattgc tggtgctggc cagccatggc ttaggactcc aacagccact ctgagggagg 12841 ggagaaggga gcagaggcca cgcagaatga accgatgggg tattcagttg ctggcagcta 12901 cattgtgtgg cattctagca tcttcaggtc tttagatctt ggacaagttg gcagggtatt 12961 ttaaaagcta taactactgt agttttccag ttttcattgc tgctttagca aaccacgctg 13021 tcttacagtg gtactttctt ctggccactg cactgtagat aattcattgg aaacaagatt 13081 tacccactac ataaaaggtt aaactccttc agtatgttgg agtggtttct tttttttttt 13141 ctttctttct tttttttctt caggtttata tcttctctaa tacctgcatg tggcgtttaa 13201 aaatcaagac cacggtcaaa cccctcttct aatcacatta attgtttcca ttctttttac 13261 cctgagtgag cacttttcac tttccagcta ggtctgtttt tcagcttgca gacaagattg 13321 agaaatcctt gaaaatttgg ttttggttaa aatttttggt ttatttattt gaaatccaca 13381 ctcccttgga aactcttaag tgcatttgtg cacttctgtt tgtttgtctc aaagaaggga 13441 ctgtaacaat ctgagtaatt tccatgtcct cttccttatt cctctagtgg ttgaagctgt 13501 gtagcatttt aacatatata tattcacaaa tatattcata taaacagtat acattttgaa 13561 tcagtcattt gttaaagaaa agtatattca atgaagatga aatttaaata aaaaaggaca 13621 gagtctatcc tccagggatt gaacattttc caattatctg gtcttttcct gttgtgcaaa 13681 aatgactcat tgctccgaat gtcaaaaaca aatgcgacaa acaatggcac ttcatcattt 13741 aaagtaatgt tgccaagaga aaaaatttcc tgggagggag gtttcccaca agccaaatct 13801 cctaagcctc aaatgctagc actttttggc agttggatag gaaatgagac attctttggc 13861 agccaaaata agagaggccg atggtgaaac tttttgagac accctatggc cttcttgtca 13921 aaaccttcac tggagctcaa gaaaagcatt tctgttgtgt tatttgcagt gcagatgatg 13981 tctgtgtaac aacataatgg ttattcacct ttttttgatt ttgatttttg ctgtgttatc 14041 aaaaacttga atactgtgag aagaagtgaa ttttcagttg acgaatcagc atcttgttcc 14101 catggtgata acactaattg aatatatcta tgagggcatg tattagttaa tggaaaaaaa 14161 aatacaacac taacaataca tagctgcaat gtgtacaatg gctgatttaa ttaaataaaa 14221 tgtacaagtg ttaaatgtgg caa

One example of a nucleic acid sequence for human ARHGAP6 is available as NCBI accession number NM_(—)013427 (gi: 95091874). This sequence is recited below for easy reference as SEQ ID NO:120.

1 ggctgggctg cgaatagcgt gttcctctcc ggcggaacac acacacccgg ccttggggct 61 gtctcctgag ctccctcctc cacggagagc gctgagcgcc gccgggaatt ccatcccacc 121 gtgggcacgc agtctttgga ggtcccgggc gcagcacgct cggtgtcccc acactgcagc 181 aagacagaga ccccgcggga accttgagct tggaacaacc cttgagcctc tgcagtcgga 241 agagtgggcg cagcagccca gcggaggcca ggcgcgcaac ctcgggcgcc ggggcaagga 301 gagagtgcag ggaggcgcag ctcaggcgcc cggctcagga gcgggaggaa gttctcgcgg 361 cgccgggagc gcggtggacg cgccctgggc gcacgcccag gcagccttct ccctggccct 421 cgggactgtc ctcgggccgc aaggaggagc ttgctggagt cttagaggcc atccagagcc 481 agcgagcagg agcgctgcgt ctcccgcctc agctaggaag ggggagtggc gctggcaggc 541 tggagctggg aacccagcga gcgcctgacc ttcctcctcc tcttcctgac cctcttcgcg 601 tcttgggctc cggaggaagg ttctagcggc tgcaggaggt ccccagaccc attttcctag 661 aaggctggtg atggatctgc tgctcctgcc gccgccgggg cacttggagc gcaccggcgg 721 cgcgtgagct gggctttgct ctccactgcc ctgggcaaac cccgggccag ccccgcctgg 781 cacctttgcc tgagtccctt tcggttcccg acccaaagcc accagcgtcc agggagggag 841 gaggaggtgg tcctcaggtg cagccccgcc gagatgtccg cgcagagcct gctccacagc 901 gtcttctcct gttcctcgcc cgcttcaagt agcgcggcct cggccaaggg cttctccaag 961 aggaagctgc gccagacccg cagcctggac ccggccctga tcggcggctg cgggagcgac 1021 gaggcgggcg cggagggcag tgcgcgggga gccacggcgg gccgcctcta ctccccatca 1081 ctcccagccg agagtctcgg ccctcgcttg gcgtcctctt cccggggtcc gccccccagg 1141 gccaccaggc taccgcctcc tggacctctt tgctcgtcct tctccacacc cagcaccccg 1201 caggagaagt caccatccgg cagctttcac tttgactatg aggttcccct gggtcgcggc 1261 ggcctcaaga agagcatggc ctgggacctg ccttctgtcc tggccgggcc agccagtagc 1321 cgaagcgctt ccagcatcct ctgttcatcc gggggaggcc ccaatggcat cttcgcttct 1381 cctaggaggt ggctccagca gaggaagttc cagtccccac ccgacagtcg cgggcacccc 1441 tacgtcgtgt ggaaatccga gggtgatttc acctggaaca gcatgtcagg ccgcagtgta 1501 cggctgaggt cagtccccat ccagagtctc tcagagctgg agagggcccg gctgcaggaa 1561 gtggcttttt atcagttgca acaggactgt gacctgagct gtcagatcac cattcccaaa 1621 gatggacaaa agagaaagaa atctttaaga aagaaactgg attcactagg aaaggagaaa 1681 aacaaagaca aagaattcat cccacaggca tttggaatgc ccttatccca agtcattgcg 1741 aatgacaggg cctataaact caagcaggac ttgcagaggg acgagcagaa agatgcatct 1801 gactttgtgg cttccctcct cccatttgga aataaaagac aaaacaaaga actctcaagc 1861 agtaactcat ctctcagctc aacctcagaa acaccgaatg agtcaacgtc cccaaacacc 1921 ccggaaccgg ctcctcgggc taggaggagg ggtgccatgt cagtggattc tatcaccgat 1981 cttgatgaca atcagtctcg actactagaa gctttacaac tttccttgcc tgctgaggct 2041 caaagtaaaa aggaaaaagc cagagataag aaactcagtc tgaatcctat ttacagacag 2101 gtccctaggc tggtggacag ctgctgtcag cacctagaaa aacatggcct ccagacagtg 2161 gggatattcc gagttggaag ctcaaaaaag agagtgagac aattacgtga ggaatttgac 2221 cgtgggattg atgtctctct ggaggaggag cacagtgttc atgatgtggc agccttgctg 2281 aaagagttcc tgagggacat gccagacccc cttctcacca gggagctgta cacagctttc 2341 atcaacactc tcttgttgga gccggaggaa cagctgggca ccttgcagct cctcatatac 2401 cttctacctc cctgcaactg cgacaccctc caccgcctgc tacagttcct ctccatcgtg 2461 gccaggcatg ccgatgacaa catcagcaaa gatgggcaag aggtcactgg gaataaaatg 2521 acatctctaa acttagccac catatttgga cccaacctgc tgcacaagca gaagtcatca 2581 gacaaagaat tctcagttca gagttcagcc cgggctgagg agagcacggc catcatcgct 2641 gttgtgcaaa agatgattga aaattatgaa gccctgttca tggttccccc agatctccag 2701 aacgaagtgc tgatcagcct gttagagacc gatcctgatg tcgtggacta tttactcaga 2761 agaaaggctt cccaatcatc aagccctgac atgctgcagt cggaagtttc cttttccgtg 2821 ggagggaggc attcatctac agactccaac aaggcctcca gcggagacat ctccccttat 2881 gacaacaact ccccagtgct gtctgagcgc tccctgctgg ctatgcaaga ggacgcggcc 2941 ccggggggct cggagaagct ttacagagtg ccagggcagt ttatgctggt gggccacttg 3001 tcgtcgtcaa agtcaaggga aagttctcct ggaccaaggc ttgggaaaga tctgtcagag 3061 gagcctttcg atatctgggg aacttggcat tcaacattaa aaagcggatc caaagaccca 3121 ggaatgacag gttcctctgg agacattttt gaaagcagct ccctaagagc ggggccctgc 3181 tccctttctc aagggaacct gtccccaaat tggcctcggt ggcaggggag ccccgcagag 3241 ctggacagcg acacgcaggg ggctcggagg actcaggccg cagcccccgc gacggagggc 3301 agggcccacc ctgcggtgtc gcgcgcctgc agcacgcccc acgtccaggt ggcagggaaa 3361 gccgagcggc ccacggccag gtcggagcag tacttgaccc tgagcggcgc ccacgacctc 3421 agcgagagtg agctggatgt ggccgggctg cagagccggg ccacacctca gtgccaaaga 3481 ccccatggga gtgggaggga tgacaagcgg cccccgcctc catacccggg cccagggaag 3541 cccgcggcag cggcagcctg gatccagggg cccccggaag gcgtggagac acccacggac 3601 cagggaggcc aagcagccga gcgagagcag caggtcacgc agaaaaaact gagcagcgcc 3661 aactccctgc cagcgggcga gcaggacagt ccgcgcctgg gggacgctgg ctggctcgac 3721 tggcagagag agcgctggca gatctgggag ctcctgtcga ccgacaaccc cgatgccctg 3781 cccgagacgc tggtctgagc ccgcacccag ccgagccccc cctgccccga gccccccgcc 3841 ctccagccca ggggggaccg tgggtggtgg ccactggcac acttagtgtt cttctttcac 3901 acttctcaaa agtgacacaa gagaaatcca gttcacctac agaggtagag cactcacgcc 3961 cccgccattg agaataaggt tccattgcgt agccagcctt aggaaaaaca aacagaaccc 4021 aaaccagatg gcaatgtcca atctaaaaac gtccctcttg gctctataat ataagataca 4081 actcttgctt ggtatagcct aaccgtattt atgtgtcttc ggttttgact attgtgtatt 4141 ctgtaacaga ttatgtataa tcatatatga tatattcaca aagagaaaac aaaaggaact 4201 tttaaaaaaa aaatcacttc acttatatta agcaatgaga tatactaaac aatgagattc 4261 tatagaatgt tctagaatgt gcacaagcgg gtttctgtgc ttttgccata gctttataac 4321 tggggataac ccttccttcg ataccaaaca ctaacaagag gaagcagaat atgagaagcc 4381 atatttttac ataggagtca gatacaaaaa gaaaaatcac tgaatgcttt tagatattga 4441 atacgttttc aggaaaatgc taaatctgat agattacgaa atatattttt agaacttgtt 4501 tagaaaggat tcagttaacc aaacaagaaa aaggcagtgc ctcacaaaga aattaagaag 4561 ttgtccgtcc cacgttacat caaattcagt tttatatagg ccatatataa tatatattta 4621 taatgtataa tttttatgta tttttcaaaa ctacaaactg gaatccaact ataaagtgtt 4681 taagaatcta cacagaatat tcaaattata gaacatgttt tttccctttg ccccataatc 4741 agtatttgcc aaattacatg caattcctta aaaactaaat cacatttggt aaaaggccta 4801 cagctttgta cttacattgt gccaaaggct gaggaaatgt tttctttcgt aattttatgt 4861 gtattgtaaa atgttctacc gtactttagt agtttgaagt ttttcaagtg cataactatt 4921 tttgaccagc agatggcgat acgcttcagt attttatgca attttttttc acttctgaag 4981 ggaaagtgta ttataaaaaa agattttttt tttttttata aaacatgcta ctcttaattt 5041 tcatgttggt gatgaaattc ccagtggtgt ttcttaaggt tctatcttgt gccatgatga 5101 ataaaaagtt aagcaaag

One example of a nucleic acid sequence for human C11orf17 is available as NCBI accession number NM_(—)182901 (gi: 116174739). This sequence is recited below for easy reference as SEQ ID NO:121.

1 agatgaaaat ggaaggggcg ggcgcgctag gcctagtcct ggctgggctc ccgctggagt 61 gtgcgttggg ggcggaccag gagcggtggt ctccagggag gtcgaggctg gggctcccac 121 ccggatttgg agcagggtcg ccgcggccca gctgacccgc cggcgtttgt acgttgtgtg 181 cccactcagg gagccatgga caactgtttg gcggccgcag cgctgaatgg ggtggaccga 241 cgttccctgc agcgttcagc aaggctggct ctagaagtgc tggagagggc caagaggagg 301 gcggtggact ggcatgccct ggagcgtccc aaaggctgca tgggggtcct tgcccgggag 361 gcgccccacc tagagaaaca gccggcagcc ggcccgcagc gcgttctccc gggagagaga 421 gaagagagac ccccaaccct tagtgcttcc ttcagaacaa tggctgaatt catggactat 481 acttcaagtc agtgtgggaa atattattca tctgtgccag aggaaggagg ggcaacccat 541 gtctatcgtt atcacagagg cgagtcgaag ctgcacatgt gcttggacat agggaatggt 601 cagagaaaag acagaaaaaa gacatccctt ggtcctggag gcagctatca aatatcagag 661 catgctccag aggcatccca gcctgctgag aacatctcta aggacctcta catagaagta 721 tatccaggga cctattctgt cactgtgggc tcaaatgact taaccaagaa gactcatgtg 781 gtagcagttg attctggaca aagcgtggac ctggtcttcc ctgtgtgatg ttgaccatca 841 ctgccatcac atcacctttt tttaagtagt aagaataaag ccactgtatg attctcttaa 901 tagctataca ttaatcctgt ttttagtgct gactgggtca gccttccggg aactggagtc 961 tgtctctttc agtgcttttt tgtttgtttg gttggttttt ttttgagaca gtctcactct 1021 gttgcccagg ctggagtgca gtggcgtgat ctcggctcac tgcaagttcc gcctcccggg 1081 ttcacaccat tctcctgcct cagcctcccg agtagctggc actacaggca cccgccacca 1141 tgcccggcta ttttttttgt atttttagta gagacggggt ttcaccatgt tggccaggat 1201 ggtctcgatc tcttgacctc gtgatccacc caccttggcc tcccaaagtg ttgggattac 1261 aggcgtgagc caccgcgccc ggcctcagtg ccttttttaa cttgagggtg tagaggtcct 1321 ccacgcttgt ttgcctgaaa gtaatataat gatgctgtct gaacaggttt tactgcttgc 1381 tttccaagta aaggttaatt atgataataa agagatttgg aaatgaa

One example of a nucleic acid sequence for human CAPN3 is available as NCBI accession number NM_(—)000070 (gi: 27765081). This sequence is recited below for easy reference as SEQ ID NO:122.

1 cactctcttt ctctctccct ctggcatgca tgctgctggt aggagacccc caagtcaaca 61 ttgcttcaga aatcctttag cactcatttc tcaggagaac ttatggcttc agaatcacag 121 ctcggttttt aagatggaca taacctgtac gaccttctga tgggctttca actttgaact 181 ggatgtggac acttttctct cagatgacag aattactcca acttcccctt tgcagttgct 241 tcctttcctt gaaggtagct gtatcttatt ttctttaaaa agctttttct tccaaagcca 301 cttgccatgc cgaccgtcat tagcgcatct gtggctccaa ggacagcggc tgagccccgg 361 tccccagggc cagttcctca cccggcccag agcaaggcca ctgaggctgg gggtggaaac 421 ccaagtggca tctattcagc catcatcagc cgcaattttc ctattatcgg agtgaaagag 481 aagacattcg agcaacttca caagaaatgt ctagaaaaga aagttcttta tgtggaccct 541 gagttcccac cggatgagac ctctctcttt tatagccaga agttccccat ccagttcgtc 601 tggaagagac ctccggaaat ttgcgagaat ccccgattta tcattgatgg agccaacaga 661 actgacatct gtcaaggaga gctaggggac tgctggtttc tcgcagccat tgcctgcctg 721 accctgaacc agcaccttct tttccgagtc ataccccatg atcaaagttt catcgaaaac 781 tacgcaggga tcttccactt ccagttctgg cgctatggag agtgggtgga cgtggttata 841 gatgactgcc tgccaacgta caacaatcaa ctggttttca ccaagtccaa ccaccgcaat 901 gagttctgga gtgctctgct ggagaaggct tatgctaagc tccatggttc ctacgaagct 961 ctgaaaggtg ggaacaccac agaggccatg gaggacttca caggaggggt ggcagagttt 1021 tttgagatca gggatgctcc tagtgacatg tacaagatca tgaagaaagc catcgagaga 1081 ggctccctca tgggctgctc cattgatgat ggcacgaaca tgacctatgg aacctctcct 1141 tctggtctga acatggggga gttgattgca cggatggtaa ggaatatgga taactcactg 1201 ctccaggact cagacctcga ccccagaggc tcagatgaaa gaccgacccg gacaatcatt 1261 ccggttcagt atgagacaag aatggcctgc gggctggtca gaggtcacgc ctactctgtc 1321 acggggctgg atgaggtccc gttcaaaggt gagaaagtga agctggtgcg gctgcggaat 1381 ccgtggggcc aggtggagtg gaacggttct tggagtgata gatggaagga ctggagcttt 1441 gtggacaaag atgagaaggc ccgtctgcag caccaggtca ctgaggatgg agagttctgg 1501 atgtcctatg aggatttcat ctaccatttc acaaagttgg agatctgcaa cctcacggcc 1561 gatgctctgc agtctgacaa gcttcagacc tggacagtgt ctgtgaacga gggccgctgg 1621 gtacggggtt gctctgccgg aggctgccgc aacttcccag atactttctg gaccaaccct 1681 cagtaccgtc tgaagctcct ggaggaggac gatgaccctg atgactcgga ggtgatttgc 1741 agcttcctgg tggccctgat gcagaagaac cggcggaagg accggaagct aggggccagt 1801 ctcttcacca ttggcttcgc catctacgag gttcccaaag agatgcacgg gaacaagcag 1861 cacctgcaga aggacttctt cctgtacaac gcctccaagg ccaggagcaa aacctacatc 1921 aacatgcggg aggtgtccca gcgcttccgc ctgcctccca gcgagtacgt catcgtgccc 1981 tccacctacg agccccacca ggagggggaa ttcatcctcc gggtcttctc tgaaaagagg 2041 aacctctctg aggaagttga aaataccatc tccgtggatc ggccagtgaa aaagaaaaaa 2101 accaagccca tcatcttcgt ttcggacaga gcaaacagca acaaggagct gggtgtggac 2161 caggagtcag aggagggcaa aggcaaaaca agccctgata agcaaaagca gtccccacag 2221 ccacagcctg gcagctctga tcaggaaagt gaggaacagc aacaattccg gaacattttc 2281 aagcagatag caggagatga catggagatc tgtgcagatg agctcaagaa ggtccttaac 2341 acagtcgtga acaaacacaa ggacctgaag acacacgggt tcacactgga gtcctgccgt 2401 agcatgattg cgctcatgga tacagatggc tctggaaagc tcaacctgca ggagttccac 2461 cacctctgga acaagattaa ggcctggcag aaaattttca aacactatga cacagaccag 2521 tccggcacca tcaacagcta cgagatgcga aatgcagtca acgacgcagg attccacctc 2581 aacaaccagc tctatgacat cattaccatg cggtacgcag acaaacacat gaacatcgac 2641 tttgacagtt tcatctgctg cttcgttagg ctggagggca tgttcagagc ttttcatgca 2701 tttgacaagg atggagatgg tatcatcaag ctcaacgttc tggagtggct gcagctcacc 2761 atgtatgcct gaaccaggct ggcctcatcc aaagccatgc aggatcactc aggatttcag 2821 tttcaccctc tatttccaaa gccatttacc tcaaaggacc cagcagctac acccctacag 2881 gcttccaggc acctcatcag tcatgctcct cctccatttt accccctacc catccttgat 2941 cggtcatgcc tagcctgacc ctttagtaaa gcaatgaggt aggaagaaca aacccttgtc 3001 cctttgccat gtggaggaaa gtgcctgcct ctggtccgag ccgcctcggt tctgaagcga 3061 gtgctcctgc ttaccttgct ctaggctgtc tgcagaagca cctgccggtg gcactcagca 3121 cctccttgtg ctagagccct ccatcacctt cacgctgtcc caccatgggc caggaaccaa 3181 accagcactg ggttctactg ctgtggggta aactaactca gtggaatagg gctggttact 3241 ttgggctgtc caactcataa gtttggctgc attttgaaaa aagctgatct aaataaaggc 3301 atgtgtatgg ctggtc

One example of a nucleic acid sequence for human CDH16 is available as NCBI accession number NM_(—)004062 (gi: 16507958). This sequence is recited below for easy reference as SEQ ID NO:123.

1 gaaggagctc tcttcttgct tggcagctgg accaagggag ccagtcttgg gcgctggagg 61 gcctgtcctg accatggtcc ctgcctggct gtggctgctt tgtgtctccg tcccccaggc 121 tctccccaag gcccagcctg cagagctgtc tgtggaagtt ccagaaaact atggtggaaa 181 tttcccttta tacctgacca agttgccgct gccccgtgag ggggctgaag gccagatcgt 241 gctgtcaggg gactcaggca aggcaactga gggcccattt gctatggatc cagattctgg 301 cttcctgctg gtgaccaggg ccctggaccg agaggagcag gcagagtacc agctacaggt 361 caccctggag atgcaggatg gacatgtctt gtggggtcca cagcctgtgc ttgtgcacgt 421 gaaggatgag aatgaccagg tgccccattt ctctcaagcc atctacagag ctcggctgag 481 ccggggtacc aggcctggca tccccttcct cttccttgag gcttcagacc gggatgagcc 541 aggcacagcc aactcggatc ttcgattcca catcctgagc caggctccag cccagccttc 601 cccagacatg ttccagctgg agcctcggct gggggctctg gccctcagcc ccaaggggag 661 caccagcctt gaccacgccc tggagaggac ctaccagctg ttggtacagg tcaaggacat 721 gggtgaccag gcctcaggcc accaggccac tgccaccgtg gaagtctcca tcatagagag 781 cacctgggtg tccctagagc ctatccacct ggcagagaat ctcaaagtcc tatacccgca 841 ccacatggcc caggtacact ggagtggggg tgatgtgcac tatcacctgg agagccatcc 901 cccgggaccc tttgaagtga atgcagaggg aaacctctac gtgaccagag agctggacag 961 agaagcccag gctgagtacc tgctccaggt gcgggctcag aattcccatg gcgaggacta 1021 tgcggcccct ctggagctgc acgtgctggt gatggatgag aatgacaacg tgcctatctg 1081 ccctccccgt gaccccacag tcagcatccc tgagctcagt ccaccaggta ctgaagtgac 1141 tagactgtca gcagaggatg cagatgcccc cggctccccc aattcccacg ttgtgtatca 1201 gctcctgagc cctgagcctg aggatggggt agaggggaga gccttccagg tggaccccac 1261 ttcaggcagt gtgacgctgg gggtgctccc actccgagca ggccagaaca tcctgcttct 1321 ggtgctggcc atggacctgg caggcgcaga gggtggcttc agcagcacgt gtgaagtcga 1381 agtcgcagtc acagatatca atgatcacgc ccctgagttc atcacttccc agattgggcc 1441 tataagcctc cctgaggatg tggagcccgg gactctggtg gccatgctaa cagccattga 1501 tgctgacctc gagcccgcct tccgcctcat ggattttgcc attgagaggg gagacacaga 1561 agggactttt ggcctggatt gggagccaga ctctgggcat gttagactca gactctgcaa 1621 gaacctcagt tatgaggcag ctccaagtca tgaggtggtg gtggtggtgc agagtgtggc 1681 gaagctggtg gggccaggcc caggccctgg agccaccgcc acggtgactg tgctagtgga 1741 gagagtgatg ccacccccca agttggacca ggagagctac gaggccagtg tccccatcag 1801 tgccccagcc ggctctttcc tgctgaccat ccagccctcc gaccccatca gccgaaccct 1861 caggttctcc ctagtcaatg actcagaggg ctggctctgc attgagaaat tctccgggga 1921 ggtgcacacc gcccagtccc tgcagggcgc ccagcctggg gacacctaca cggtgcttgt 1981 ggaggcccag gatacagatg agccgagact gagcgcttct gcacccctgg tgatccactt 2041 cctaaaggcc cctcctgccc cagccctgac tcttgcccct gtgccctccc aatacctctg 2101 cacaccccgc caagaccatg gcttgatcgt gagtggaccc agcaaggacc ccgatctggc 2161 cagtgggcac ggtccctaca gcttcaccct tggtcccaac cccacggtgc aacgggattg 2221 gcgcctccag actctcaatg gttcccatgc ctacctcacc ttggccctgc attgggtgga 2281 gccacgtgaa cacataatcc ccgtggtggt cagccacaat gcccagatgt ggcagctcct 2341 ggttcgagtg atcgtgtgtc gctgcaacgt ggaggggcag tgcatgcgca aggtgggccg 2401 catgaagggc atgcccacga agctgtcggc agtgggcatc cttgtaggca ccctggtagc 2461 aataggaatc ttcctcatcc tcattttcac ccactggacc atgtcaagga agaaggaccc 2521 ggatcaacca gcagacagcg tgcccctgaa ggcgactgtc tgaatggccc aggcagctct 2581 agctgggagc ttggcctctg gctccatctg agtcccctgg gagagagccc agcacccaag 2641 atccagcagg ggacaggaca gagtagaagc ccctccatct gccctggggt ggaggcacca 2701 tcaccatcac caggcatgtc tgcagagcct ggacaccaac tttatggact gcccatggga 2761 gtgctccaaa tgtcagggtg tttgcccaat aataaagccc cagagaactg ggctgggccc 2821 tatgggattg gta

One example of a nucleic acid sequence for human ChGn is available as NCBI accession number BC060772 (gi: 38174239). This sequence is recited below for easy reference as SEQ ID NO:124.

1 tggggcttgt tccgggatcc gcagccttgc tcaggctgtg cattggtgtg gccccgaatt 61 gcacggagct gccttcctat ttcaaggaaa gacgccaagg taattttgac ccagaggagc 121 aatgatgtag ccacctccta accttccctt cttgaacccc caggtcccct cttgctgttg 181 gctgcacatc aggaaggctg tgatgggaat gaaggtgaaa acttggagat ttcacttcag 241 tcattgcttc tgcctgcaag atcatccttt aaaagtagag aagctgctct gtgtggtggt 301 taactccaag aggcagaact cgttctagaa ggaaatggat gcaagcagct ccgggggccc 361 caaacgcatg cttcctgtga tctagcccag ggaagccctt ccgtgggggc cccggctttg 421 agggatgcca ccggttctgg acgcatggct gattcctgaa tgatgatggt tcgccggggg 481 ctgcttgcgt ggatttcccg ggtggtggtt ttgctggtgc tcctctgctg tgctatctct 541 gtcctgtaca tgttggcctg caccccaaaa ggtgacgagg agcagctggc actgcccagg 601 gccaacagcc ccacggggaa ggaggggtac caggccgtcc ttcaggagtg ggaggagcag 661 caccgcaact acgtgagcag cctgaagcgg cagatcgcac agctcaagga ggagctgcag 721 gagaggagtg agcagctcag gaatgggcag taccaagcca gcgatgctgc tggcctgggt 781 ctggacagga gccccccaga gaaaacccag gccgacctcc tggccttcct gcactcgcag 841 gtggacaagg cagaggtgaa tgctggcgtc aagctggcca cagagtatgc agcagtgcct 901 ttcgatagct ttactctaca gaaggtgtac cagctggaga ctggccttac ccgccacccc 961 gaggagaagc ctgtgaggaa ggacaagcgg gatgagttgg tggaagccat tgaatcagcc 1021 ttggagaccc tgaacaatcc tgcagagaac agccccaatc accgtcctta cacggcctct 1081 gatttcatag aagggatcta ccgaacagaa agggacaaag ggacattgta tgagctcacc 1141 ttcaaagggg accacaaaca tgaattcaaa cggctcatct tatttcgacc attcggcccc 1201 atcatgaaag tggaaaatga aaagctcaac atggccaaca cgcttatcaa tgttatcgtg 1261 cctctagcaa aaagggtgga caagttccgg cagttcatgc agaatttcag gcctgctgat 1321 gaagttttta gatgtgtgcc tttaagccct tgattgtgcg gtgttggatc ttagaagctg 1381 tgatggctca gatgcacata ttggctgagg ataaccagct aagtgatttc accagcttgt 1441 tttaaacata gaaaatccta ctgtctaatt ataaatcttg aaagatcaag ctgatttttt 1501 atttcttttt ttttgagatg gagtcttact ctgtcaccca ggctggagtg cagtggcacg 1561 aactctgctc actgcaacct tcacctccca ggttcaggga gatgtgcatt gagcaggatg 1621 ggagagtcca tctcactgtt gtttactttg ggaaagaaga aataaatgaa gtcaaaggaa 1681 tacttgaaaa cacttccaaa gctgccaact tcaggaactt taccttcatc cagctgaatg 1741 gagaattttc tcggggaaag ggacttgatg ttggagcccg cttctggaag ggaagcaacg 1801 tccttctctt tttctgtgat gtggacatct acttcacatc tgaattcctc aatacgtgta 1861 ggctgaatac acagccaggg aagaaggtat tttatccagt tcttttcagt cagtacaatc 1921 ctggcataat atacggccac catgatgcag tccctccctt ggaacagcag ctggtcataa 1981 agaaggaaac tggattttgg agagactttg gatttgggat gacgtgtcag tatcggtcag 2041 acttcatcaa tataggtggg tttgatctgg acatcaaagg ctggggcgga gaggatgtgc 2101 acctttatcg caagtatctc cacagcaacc tcatagtggt acggacgcct gtgcgaggac 2161 tcttccadct ctggcatgag aagcgctgca tggacgagct gacccccgag cagtacaaga 2221 tgtgcatgca gtccaaggcc atgaacgagg catcccacgg ccagctgggc atgctggtgt 2281 tcaggcacga gatagaggct caccttcgca aacagaaaca gaagacaagt agcaaaaaaa 2341 catgaactcc cagagaagga ttgtgggaga cactttttct ttccttttgc aattactgaa 2401 agtggctgca acagagaaaa gacttccata aaggacgaca aaagaattgg actgatgggt 2461 cagagatgag aaagcctccg atttctctct gttgggcttt ttacaacaga aatcaaaatc 2521 tccgctttgc ctgcaaaagt aacccagttg caccctgtga agtgtctgac aaaggcagaa 2581 tgcttgtgag attataagcc taatggtgtg gaggttttga tggtgtttac aatacactga 2641 gacctgttgt tttgtgtgct cattgaaata ttcatgattt aagagcagtt ttgtaaaaaa 2701 ttcattagca tgaaaggcaa gcatatttct cctcatatga atgagcctat cagcagggct 2761 ctagtttcta ggaatgctaa aatatcagaa ggcaggagag gagataggct tattatgata 2821 ctagtgagta cattaagtaa aataaaatgg accagaaaag aaaagaaacc ataaatatcg 2881 tgtcatattt tccccaagat taaccaaaaa taatctgctt atctttttgg ttgtcctttt 2941 aactgtctcc gtttttttct tttatttaaa aatgcacttt ttttcccttg tgagttatag 3001 tctgcttatt taattaccac tttgcaagcc ttacaagaga gcacaagttg gcctacattt 3061 ttatattttt taagaagata ctttgagatg cattatgaga actttcagtt caaagcatca 3121 aattgatgcc atatccaagg acatgccaaa tgctgattct gtcaggcact gaatgtcagg 3181 cattgagaca tagggaagga atggtttgta ctaatacaga cgtacagata ctttctctga 3241 agagtatttt cgaagaggag caactgaaca ctggaggaaa agaaaatgac actttctgct 3301 ttacagaaaa ggaaactcat tcagactggt gatatcgtga tgtacctaaa agtcagaaac 3361 cacattttct cctcagaagt agggaccgct ttcttacctg tttaaataaa ccaaagtata 3421 ccgtgtgaac caaacaatct cttttcaaaa cagggtgctc ctcctggctt ctggcttcca 3481 taagaagaaa tggagaaaaa tatatatata tatatatata ttgtgaaaga tcaatccatc 3541 tgccagaatc tagtgggatg gaagtttttg ctacatgtta tccaccccag gccaggtgga 3601 agtaactgaa ttatttttta aattaagcag ttctactcga tcaccaagat gcttctgaaa 3661 attgcatttt attaccattt caaactattt tttaaaaata aatacagtta acatagagtg 3721 gtttcttcat tcatgtgaaa attattagcc agcaccagat gcatgagcta attatctctt 3781 tgagtccttg cttctgtttg ctcacagtaa actcattgtt taaaagcttc aagaacattc 3841 aagctgttgg tgtgttaaaa aatgcattgt attgatttgt actggtagtt tatgaaattt 3901 aattaaaaca caggccatga atggaaggtg gtattgcaca gctaataaaa tatgatttg 3961 ggatatgaaa aaaaaaaaaa aa

One example of a nucleic acid sequence for human CITED1 is available as NCBI accession number NM_(—)004143 (gi: 222136685). This sequence is recited below for easy reference as SEQ ID NO:125.

1 acgagccagg acatgtgcta ataatgccct aagccggtta taaagacgtg gaaattgagg 61 ggagaaaaaa aaagggaaaa aaagggtctg tccttcctgg gattcctagc cgaggccagt 121 ctgctgccgt gtgcgtgtgc gtcagggctc tccgggcggc aatgggggct tgagagccgg 181 gtccccagcg ccgggaaggg agcgcggtgg ccgccaccgc caccgccccg gagtccggcg 241 ccgaagctgc gggcgggcgg gcgggcacca gctcggtcag gggctgcttg gcgcggcact 301 gtgcggtgca gcggcggcgc ggcgcggtgc gggcttttcc caggcgcccc ggggtcgggt 361 ggccaacggc gcggccgcgg gcgctgagcg cgaccggttc gcggtagcgg tggcggcggc 421 gtgcgtgcca ggggctgggg gctccgccgc ctctcttgcg gctcaccgag ctccgcgctt 481 ccctctctcc agggcaggcg gcttctcaga gcacaacagc tccagctggc agcatcactt 541 cccgccaatt tatccaactt ctgccaaggc tctgaaatgc caacaacgtc gaggcctgca 601 cttgatgtca agggtggcac ctcacctgcg aaggaggatg ccaaccaaga gatgagctcc 661 gtggcctact ccaaccttgc ggtgaaagat cgcaaagcag tggccattct gcactaccct 721 ggggtagcct caaatggaac caaggccagt ggggctccca ctagttcctc gggatctcca 781 ataggctctc ctacaaccac ccctcccact aaacccccat ccttcaacct gcaccccgcc 841 cctcacttgc tggctagtat gcacctgcag aaacttaata gccagtatca ggggatggct 901 gctgccactc caggccaacc cggggaggca ggacccctgc aaaactggga ctttggggcc 961 caggcgggag gggcagaatc actctctcct tctgctggtg cccagagccc tgctatcatc 1021 gattcggacc cagtggatga ggaagtgctg atgtcgctgg tggtggaact ggggttggac 1081 cgagccaatg agcttccgga gctgtggctg gggcagaatg agtttgactt cactgcggac 1141 tttccatcta gctgctaatg ccaagtgtcc ctaaagatgg aggaataaag ccaccaattc 1201 tgttgtaaat aaaaataaag ttacttacaa agagacgggc caaaaaaaaa a

One example of a nucleic acid sequence for human CITED2 is available as NCBI accession number NM_(—)006079 (gi: 51807294). This sequence is recited below for easy reference as SEQ ID NO:126.

1 acagctcatt gttggcagct gccgggcggt cctgccgagc tgtgagggca acggagggga 61 aataaaaggg aacggctccg aatctgcccc agcggccgct gcgagacctc ggcgccgaca 121 tcgcgacagc gaagcgcttt gcacgccagg aaggtcccct ctatgtgctg ctgagccggt 181 cctggacgcg acgagcccgc cctcggtctt cggagcagaa atcgcaaaaa cggaaggact 241 ggaaatggca gaccatatga tggccatgaa ccacgggcgc ttccccgacg gcaccaatgg 301 gctgcaccat caccctgccc accgcatggg catggggcag ttcccgagcc cccatcacca 361 ccagcagcag cagccccagc acgccttcaa cgccctaatg ggcgagcaca tacactacgg 421 cgcgggcaac atgaatgcca cgagcggcat caggcatgcg atggggccgg ggactgtgaa 481 cggagggcac cccccgagcg cgctggcccc cgcggccagg tttaacaact cccagttcat 541 gggtcccccg gtggccagcc agggaggctc cctgccggcc agcatgcagc tgcagaagct 601 caacaaccag tatttcaacc atcaccccta cccccacaac cactacatgc cggatttgca 661 ccctgctgca ggccaccaga tgaacgggac aaaccagcac ttccgagatt gcaaccccaa 721 gcacagcggc ggcagcagca cccccggcgg ctcgggcggc agcagcaccc ccggcggctc 781 tggcagcagc tcgggcggcg gcgcgggcag cagcaacagc ggcggcggca gcggcagcgg 841 caacatgccc gcctccgtgg cccacgtccc cgctgcaatg ctgccgccca atgtcataga 901 cactgatttc atcgacgagg aagttcttat gtccttggtg atagaaatgg gtttggaccg 961 catcaaggag ctgcccgaac tctggctggg gcaaaacgag tttgatttta tgacggactt 1021 cgtgtgcaaa cagcagccca gcagagtgag ctgttgactc gatcgaaacc ccggcgaaag 1081 aaatcaaacc cccaacttct tcggcgtgaa ttaaaagaaa cattccctta gacacagtat 1141 ctcacttttc agatcttgaa aggtttgaga acttggaaac aaagtaaact ataaacttgt 1201 acaaattggt tttaaaaaaa attgctgcca cttttttttc ctgtttttgt ttcgtttttg 1261 tagccttgac attcacccac ctcccttatg tagttgaaat atctagctaa cttggtcttt 1321 ttcgttgttt gtttttactc ctttccctca ctttctccag tgctcaactg ttagatatta 1381 atcttggcaa actgcttaat cttgtggatt ttgtagatgg tttcaaatga ctgaactgca 1441 ttcagattta cgagtgaaag gaaaaattgc attagttggt tgcatgaact tcgaagggca 1501 gatattactg cacaaactgc catctcgctt cattttttta actatgcatt tgagtacaga 1561 ctaattttta aaatatgcta aactggaaga ttaaacagat gtgggccaaa ctgttctgga 1621 tcaggaaagt catactgttc actttcaagt tggctgtccc ccccgccgcc ccccccaccc 1681 ccatatgtac agatgataat agggtgtgga atgtcgtcag tggcaaacat ttcacagatt 1741 tttattttgt ttctgtcttc aacatttttg acactgtgct aatagttata ttcagtacat 1801 gaaaagatac tactgtgttg aaagcttttt aggaaatttt gacagtattt ttgtacaaaa 1861 catttttttg aaaaaatact tgttaattta ttctatttta atttgccaat gtcaataaaa 1921 agttaagaaa

One example of a nucleic acid sequence for human CKB is available as NCBI accession number M16451 (gi: 180571). This sequence is recited below for easy reference as SEQ ID NO:127.

1 ccggccgccc gcccgccgcc gccatgccct tctccaacag ccacaacgca ctgaagctgc 61 gcttcccggc cgaggacgag ttccccgacc tgagcgccca caacaaccac atggccaagg 121 tgctgacccc cgagctgtac gcggacgtgc gcgccaagag cacgccgagc ggcttcacgc 181 tggacgacgt catccagaca ggcgtggaca acccgggcca cccgtacatc atgaccgtgg 241 gctgcgtggc gggcgacgag gagtcctacg aagtgttcaa ggatctcttc gaccccatca 301 tcgaggaccg gcaccggcgc tacaagccca gcgatgacga caagaccgac ctcaaccccg 361 acaacctgca gggcggcgac gacctggacc ccaactacgt gctgagctcg cgggtggcca 421 cgggccgcag catccgtggc ttctgcctcc ccccgcactg cagccgcggg gagcgccgag 481 ccatcgagaa gctcgcggtg gaagccctgt ccagcctgga cggcgacctg gcgggccgat 541 actacgcgct caagagcatg acggaggcgg agcagcagca gctcatcgac gaccacttcc 601 tcttcgacaa gcccgtgtcg cccctgctgc tggcctcggg catggcccgc gactggcccg 661 acgccgcgcg tatctggcac aatgacaata agaccttcct ggtgtgggtc aacgaggagg 721 accacctgcg ggtcatctcc atgcagaagg ggggcaacat gaaggaggtg ttcacccgct 781 tctgcaccgg cctcacccag attgaaactc tcttcaagtc taaggactat gagttcatgt 841 ggaaccctca cctgggctac atcctcacct gcccatccaa cctgggcacc gggctgcggg 901 caggtgtcga tatcaagctg cccaacctgg gcaagcatga gaagttctcg gaggtgctta 961 agcggctgcg acttcagaag cgaggcacag gcggtgtgga cacggctgcg gtgggcgggg 1021 tcttcgacgt ctccaacgct gaccgcctgg gcttctcaga ggtggagctg gtgcagatgg 1081 tggtggacgg agtgaagctg ctcatcgaga tggaacagcg gctggagcag ggccaggcca 1141 tcgacgacct catgcctgcc cagaaatgaa gcccggccca cacccgacac cagccctgct 1201 gcttcctaac ttattgcctg cagtgcccac catgcacccc tcgatgttgc cgtctggcga 1261 gcccttagcc ttgctgtaag gaaggcttcc gtcacccttg gtagagttta tttttttgat 1321 ggctaagata ctgctgatgc tgaaataaac tagggttttg gcctgcaaaa aa

One example of a nucleic acid sequence for human COL9A3 is available as NCBI accession number NM_(—)001853 (gi: 119508425). This sequence is recited below for easy reference as SEQ ID NO:128.

1 gccatggccg ggccgcgcgc gtgcgccccg ctcctgctcc tgctcctgct cggggagctt 61 ctggcggccg ccggggcgca gagagtggga ctccccggcc cccccggccc cccagggccg 121 cccgggaagc ccggccagga cggcattgac ggagaagctg gtcctccagg tctgcctggg 181 cccccgggac caaagggggc cccaggaaag ccggggaaac caggagaggc tgggctgccg 241 ggactgccgg gtgtggatgg tctgactgga cgagatggac cccctggacc caagggtgcc 301 cctggggaac ggggaagtct gggacccccg gggccgcccg ggctgggggg caaaggcctc 361 cctggacccc ccggagaggc aggagtgagc ggccccccag gtgggatcgg cctccgcggc 421 cccccgggac cttctggact ccccggcctc cctggtcccc caggacctcc cggaccccct 481 ggacacccag gagtcctccc tgaaggcgct actgaccttc agtgcccaag tatctgcccg 541 ccaggtcccc cagggccccc tggaatgcca gggttcaagg gacccactgg ctacaaaggc 601 gagcaggggg aagtcggcaa ggacggcgag aagggtgacc ctggcccccc tgggcccgcc 661 ggcctcccgg gcagcgtggg gctgcagggc ccccggggat tacgaggact gccagggcca 721 ctcgggcccc ctggggaccg gggtcccatt gggttccgag ggccgcctgg gatcccagga 781 gcgcctggga aagcgggtga ccgaggcgag aggggcccag aagggttccg cggccccaag 841 ggtgacctcg gcagacctgg tcccaaggga acccccggag tggccgggcc aagcggagag 901 ccgggcatgc cgggcaagga cggccagaat ggcgtgccag gactcgatgg ccagaaggga 961 gaggctggtc gcaacggtgc tccgggagag aagggcccca acgggctgcc gggcctccct 1021 ggacgagcgg ggtccaaagg cgagaaggga gaacggggca gagctgggga gctgggtgag 1081 gccggcccct ctggagagcc aggcgtccct ggagatgctg gcatgcctgg ggagcgcggt 1141 gaggctggcc accggggctc agcgggggcc ctcggcccac aaggccctcc cggagcccct 1201 ggtgtccgag gcttccaggg ccagaagggc agcatgggag accccggcct tccaggcccc 1261 cagggcctcc gaggtgacgt gggcgaccgg ggtccgggag gtgccgcagg ccctaaggga

One example of a nucleic acid sequence for human CSRP2 is available as NCBI accession number NM_(—)001321 (gi: 4503100). This sequence is recited below for easy reference as SEQ ID NO:129.

1 gggatctcgg actccctgga ccctccctcc agcccagcct cgctagctcc gcctgcggta 61 cgtgctcccg cctccgactc aaaatgcctg tctggggagg tggaaacaag tgtggggcct 121 gtgggaggac cgtgtaccac gcagaagagg tgcagtgtga tggcaggagc ttccaccgct 181 gctgctttct ctgcatggtt tgcaggaaaa atttagatag cacaacagtg gcaattcacg 241 atgaagagat ctactgcaaa tcctgctacg gaaagaagta tgggccaaaa ggctacggtt 301 atggccaggg cgctggcacg cttaacatgg accgtggcga gaggctgggc atcaaaccag 361 agagtgttca gcctcacagg cctacaacaa atccaaacac ttctaaattt gctcagaaat 421 atggaggtgc tgagaagtgt tccagatgtg gggattctgt atatgctgcc gagaagataa 481 ttggagctgg aaagccctgg cacaaaaact gtttccgatg tgcaaagtgt gggaagagtc 541 ttgaatcaac aactctgact gaaaaagaag gtgaaatcta ttgtaaagga tgctatgcaa 601 agaactttgg gcccaaggga tttggctatg gccaaggagc aggggctctt gttcatgccc 661 agtaagatgt aaaccctgaa ctaaacatca cacactgaga atctcttcat aatctaggca 721 cagataatct ttaacactaa actactgtga aattctacca gcattaagta ctgtatatcg 781 ccctgtactt ggataggctg gctaactcgt aggaagagag cactgtatgg tatccttttg 841 ctttattcac cagcattttg ggggaacatt tcttttacat tttaaataaa acttcagctt 901 g

One example of a nucleic acid sequence for human DAPK2 is available as NCBI accession number NM_(—)0014326 (gi: 71774012). This sequence is recited below for easy reference as SEQ ID NO:130.

1 gaccgcggca gctcagcctc ccgccgattg tatgttccag gcctcaatga ggagtccaaa 61 catggagcca ttcaagcagc agaaggtgga ggacttttat gacatcggag aggagctggg 121 gagtggccag tttgccatcg tgaagaagtg ccgggagaag agcacggggc ttgagtatgc 181 agccaagttc atcaagaagc ggcagagccg ggcgagccgg cgcggtgtga gccgggagga 241 gatcgagcgg gaggtgagca tcctgcggca ggtgctgcac cacaatgtca tcacgctgca 301 cgacgtctat gagaaccgca ccgacgtggt gctcatcctt gagctagtgt ctggaggaga 361 gctcttcgat ttcctggccc agaaggagtc actgagtgag gaggaggcca ccagcttcat 421 taagcagatc ctggatgggg tgaactacct tcacacaaag aaaattgctc actttgatct 481 caagccagaa aacattatgt tgttagacaa gaatattccc attccacaca tcaagctgat 541 tgactttggt ctggctcacg aaatagaaga tggagttgaa tttaagaata tttttgggac 601 gccggaattt gttgctccag aaattgtgaa ctacgagccc ctgggtctgg aggctgacat 661 gtggagcata ggcgtcatca cctacatcct cttaagtgga gcatcccctt tcctgggaga 721 cacgaagcag gaaacactgg caaatatcac agcagtgagt tacgactttg atgaggaatt 781 cttcagccag acgagcgagc tggccaagga ctttattcgg aagcttctgg ttaaagagac 841 ccggaaacgg ctcacaatcc aagaggctct cagacacccc tggatcacgc cggtggacaa 901 ccagcaagcc atggtgcgca gggagtctgt ggtcaatctg gagaacttca ggaagcagta 961 tgtccgcagg cggtggaagc tttccttcag catcgtgtcc ctgtgcaacc acctcacccg 1021 ctcgctgatg aagaaggtgc acctgaggcc ggatgaggac ctgaggaact gtgagagtga 1081 cactgaggag gacatcgcca ggaggaaagc cctccaccca cggaggagga gcagcacctc 1141 ctaactggcc tgacctgcag tggccgccag ggaggtctgg gcccagcggg gctcccttct 1201 gtgcagactt ttggacccag ctcagcacca gcacccgggc gtcctgagca ctttgcaaga 1261 gagatgggcc caaggaattc agaagagctt gcaggcaagc caggagaccc tgggagctgt 1321 ggctgtcttc tgtggaggag gctccagcat tcccaaagct cttaattctc cataaaatgg 1381 gctttcctct gtctgccatc ctcagagtct ggggtgggag tgtggactta ggaaaacaat 1441 ataaaggaca tcctcatcat cacggggtga aggtcagact aaggcagcct tcttcacagg 1501 ctgagggggt tcagaaccag cctggccaaa aattacacca gagagacaga gtcctcccca 1561 ttgggaacag ggtgattgag gaaagtgaac cttgggtgtg agggaccaat cctgtgacct 1621 cccagaacca tggaagccag gacgtcaggc tgaccaacac ctcagacctt ctgaagcagc 1681 ccattgctgg cccgccatgt tgtaattttg ctcattttta ttaaacttct ggtttacctg 1741 atgcttggct tcttttaggg ctacccccat ctcatttcct ttagcccgtg tgcctgtaac 1801 tctgaggggg ggcacccagt ggggtgctga gtgggcagaa tctcagaagg tcctcctgaa 1861 ccgtccgcgc aggcctgcag tgggcctgcc tcctccttgc ttccctaaca ggaaggtgtc 1921 cagttcaaga gaacccaccc agagactggg agtggtggct cacgcctata atccctgcgc 1981 tttggcagtc cgaggcaggg gaattgcttg aactcaggag ttggagacca gcctgggcaa 2041 catggcaaaa cgcagtctgt acaaaaaata caaaaaatta gccaggtgta ggggtaggca 2101 cctggcatcc cagctactcc aggggctgag gtgacagcat tgcttaagcc cagaaggtcg 2161 aggctgcagt gagctgagat cacgccactg cactccagtc tgggtgacag agagagacca 2221 tatccaaaaa aaaaaaaagt tgccagagac gagtatgccc atgctccctc tacctcactg 2281 ccaccactcc tgctgttagg agctgagtgt gtctccctaa aatttctatg ttgaagtctt 2341 aacccttggt accacagaat atcactgtat ttggagatgg ggtctttaga aaggcactta 2401 aattaaaatg agctcactga tatgggcccc gatgcaatat aattggtgtc cttataagaa 2461 ggggaggtta ggacacgcag gaaagaccac atgaaggccc aggagtggga gggggaatag 2521 ccatcgacaa actaaggggg cctcagagga aaccaaccct gctgacacct caatcttaga 2581 ctctggcctc aaaaattgta agaaaataaa cttctgtctt ttaagcca

One example of a nucleic acid sequence for human DIO1 is available as NCBI accession number NM_(—)00972 (gi: 89357933). This sequence is recited below for easy reference as SEQ ID NO:131.

1 gagcttactc tggctttgcc gagatggggc tgccccagcc agggctgtgg ctgaagaggc 61 tctgggtgct cttggaggtg gctgtgcatg tggtcgtggg taaagtgctt ctgatattgt 121 ttccagacag agtcaagcgg aacatcctgg ccatgggcga gaagacgggt atgaccagga 181 acccccattt cagccacgac aactggatac caaccttttt cagcacccag tatttctggt 241 tcgtcttgaa ggtccgttgg cagcgactag aggacacgac tgagctaggg ggtctggccc 301 caaactgccc ggtggtccgc ctctcaggac agaggtgcaa catttgggag tttatgcaag 361 gtaataggcc actggtgctg aattttggaa gttgtacctg accttcattt atgttcaaat 421 ttgaccagtt caagaggctt attgaagact ttagttccat agcagatttt cttgtcattt 481 acattgaaga agcacatgca tcagatggct gggcttttaa gaacaacatg gacatcagaa 541 atcaccagaa ccttcaggat cgcctgcagg cagcccatct actgctggcc aggagccccc 601 agtgccctgt ggtggtggac accatgcaga accagagcag ccagctctac gcagcactgc 661 ctgagaggct ctacataatc caggagggca ggatcctcta caagggtaaa tctggccctt 721 ggaactacaa cccagaggaa gttcgtgctg ttctggaaaa gctccacagt taatctggac 781 agatacctca attctaggtg accaacggga gggcttctca aggcttagct ctccctgaga 841 cccagctggc ttttaccctt gacctgtgtc cctagctgaa tcactagctc agatttttct 901 gatctaagca aacaactccc agctgaggaa tgcaggccac agcacccaat caagacaaat 961 tgttattatc agaaaatgaa gcaacacttg agctgttcag gccagttccc tgttgaagaa 1021 acagttccct gttgaagaaa gtagagcctg acactgctcc cactttggag accacattcc 1081 ctgcacacgg tctttgagag agcagttgca ctctacaggc acacttctga ggtacggtat 1141 ctctctccag ccactctgat accaagtaat tcaagctggc attccttcta ttagggaaat 1201 tcattttacc caatttgcat ttatggaatt gatcatttaa gacactaaat tagtttttag 1261 aaccaattat gggaagaatt ccagttgtta ggaagagatg aggagttgga agaggaggga 1321 ttagaaacag gaggaggcag tcatcctctc cttgccaaaa gatttaaacc tgtccacatt 1381 ggtggtgatg atgggtgagt ttccatggta acacatccct aattttacca gggaagagga 1441 gagtactcac tttaccatct ttgaatatat ttcatagaaa tctagctctc tgtaccctga 1501 aatcttccac tagcctcact tttcaacaga gtcatctaga agggagggtt ggcttcccaa 1561 aagcataacc ttgaccaaac caaacaatag gcaccagcaa tgctgtcatt cagttatgca 1621 gaagctcatt tgtgaaattc tgtttctctg atttcttcgc aagtctctta atggtcattt 1681 gtgttagatt acatcaaact gatggatagc cattggtatt catctatttt aactctgtgt 1741 ctttacatat ttgtttatga tggccacagc ctaaagtaca cacggctgtg acttgattca 1801 aaagaaaatg ttataagatg cagtaaacta ataacagaat tattaaaata tatcaggcta 1861 aaaaaaaaaa aaaaaa

One example of a nucleic acid sequence for human DPP4 is available as NCBI accession number NM_(—)001935 (gi: 47078262). This sequence is recited below for easy reference as SEQ ID NO:132.

1 ctttcactgg caagagacgg agtcctgggt ttcagttcca gttgcctgcg gtgggctgtg 61 tgagtttgcc aaagtcccct gccctctctg ggtctcggtt ccctcgcctg tccacgtgag 121 gttggaggag ctgaacgccg acgtcatttt tagctaagag ggagcagggt ccccgagtcg 181 ccggcccagg gtctgcgcat ccgaggccgc gcgccctttc ccctccccca cggctcctcc 241 gggccccgca ctctgcgccc cggctgccgc ccagcgccct acaccgccct cagggggccc 301 tcgcgggctc cccccggccg ggatgccagt gccccgcgcc acgcgcgcct gctcccgcgc 361 cgcctgccct gcagcctgcc cgcggcgcct ttatacccag cgggctcggc gctcactaat 421 gtttaactcg gggccgaaac ttgccagcgg cgagtgactc caccgcccgg agcagcggtg 481 caggacgcgc gtctccgccg cccgcggtga cttctgcctg cgctccttct ctgaacgctc 541 acttccgagg agacgccgac gatgaagaca ccgtggaagg ttcttctggg actgctgggt 601 gctgctgcgc ttgtcaccat catcaccgtg cccgtggttc tgctgaacaa aggcacagat 661 gatgctacag ctgacagtcg caaaacttac actctaactg attacttaaa aaatacttat 721 agactgaagt tatactcctt aagatggatt tcagatcatg aatatctcta caaacaagaa 781 aataatatct tggtattcaa tgctgaatat ggaaacagct cagttttctt ggagaacagt 841 acatttgatg agtttggaca ttctatcaat gattattcaa tatctcctga tgggcagttt 901 attctcttag aatacaacta cgtgaagcaa tggaggcatt cctacacagc ttcatatgac 961 atttatgatt taaataaaag gcagctgatt acagaagaga ggattccaaa caacacacag 1021 tgggtcacat ggtcaccagt gggtcataaa ttggcatatg tttggaacaa tgacatttat 1081 gttaaaattg aaccaaattt accaagttac agaatcacat ggacggggaa agaagatata 1141 atatataatg gaataactga ctgggtttat gaagaggaag tcttcagtgc ctactctgct 1201 ctgtggtggt ctccaaacgg cactttttta gcatatgccc aatttaacga cacagaagtc 1261 ccacttattg aatactcctt ctactctgat gagtcactgc agtacccaaa gactgtacgg 1321 gttccatatc caaaggcagg agctgtgaat ccaactgtaa agttctttgt tgtaaataca 1381 gactctctca gctcagtcac caatgcaact tccatacaaa tcactgctcc tgcttctatg 1441 ttgatagggg atcactactt gtgtgatgtg acatgggcaa cacaagaaag aatttctttg 1501 cagtggctca ggaggattca gaactattcg gtcatggata tttgtgacta tgatgaatcc 1561 agtggaagat ggaactgctt agtggcacgg caacacattg aaatgagtac tactggctgg 1621 gttggaagat ttaggccttc agaacctcat tttacccttg atggtaatag cttctacaag 1681 atcatcagca atgaagaagg ttacagacac atttgctatt tccaaataga taaaaaagac 1741 tgcacattta ttacaaaagg cacctgggaa gtcatcggga tagaagctct aaccagtgat 1801 tatctatact acattagtaa tgaatataaa ggaatgccag gaggaaggaa tctttataaa 1861 atccaactta gtgactatac aaaagtgaca tgcctcagtt gtgagctgaa tccggaaagg 1921 tgtcagtact attctgtgtc attcagtaaa gaggcgaagt attatcagct gagatgttcc 1981 ggtcctggtc tgcccctcta tactctacac agcagcgtga atgataaagg gctgagagtc 2041 ctggaagaca attcagcttt ggataaaatg ctgcagaatg tccagatgcc ctccaaaaaa 2101 ctggacttca ttattttgaa tgaaacaaaa ttttggtatc agatgatctt gcctcctcat 2161 tttgataaat ccaagaaata tcctctacta ttagatgtgt atgcaggccc atgtagtcaa 2221 aaagcagaca ctgtcttcag actgaactgg gccacttacc ttgcaagcac agaaaacatt 2281 atagtagcta gctttgatgg cagaggaagt ggttaccaag gagataagat catgcatgca 2341 atcaacagaa gactgggaac atttgaagtt gaagatcaaa ttgaagcagc cagacaattt 2401 tcaaaaatgg gatttgtgga caacaaacga attgcaattt ggggctggtc atatggaggg 2461 tacgtaacct caatggtcct gggatcggga agtggcgtgt tcaagtgtgg aatagccgtg 2521 gcgcctgtat cccggtggga gtactatgac tcagtgtaca cagaacgtta catgggtctc 2581 ccaactccag aagacaacct tgaccattac agaaattcaa cagtcatgag cagagctgaa 2641 aattttaaac aagttgagta cctccttatt catggaacag cagatgataa cgttcacttt 2701 cagcagtcag ctcagatctc caaagccctg gtcgatgttg gagtggattt ccaggcaatg 2761 tggtatactg atgaagacca tggaatagct agcagcacag cacaccaaca tatatatacc 2821 cacatgagcc acttcataaa acaatgtttc tctttacctt agcacctcaa aataccatgc 2881 catttaaagc ttattaaaac tcatttttgt tttcattatc tcaaaactgc actgtcaaga 2941 tgatgatgat ctttaaaata cacactcaaa tcaagaaact taaggttacc tttgttccca 3001 aatttcatac ctatcatctt aagtagggac ttctgtcttc acaacagatt attaccttac 3061 agaagtttga attatccggt cgggttttat tgtttaaaat catttctgca tcagctgctg 3121 aaacaacaaa taggaattgt ttttatggag gctttgcata gattccctga gcaggatttt 3181 aatctttttc taactggact ggttcaaatg ttgttctctt ctttaaaggg atggcaagat 3241 gtgggcagtg atgtcactag ggcagggaca ggataagagg gattagggag agaagatagc 3301 agggcatggc tgggaaccca agtccaagca taccaacacg agcaggctac tgtcagctcc 3361 cctcggagaa gagctgttca cagccagact ggcacagttt tctgagaaag actattcaaa 3421 cagtctcagg aaatcaaata tgcaaagcac tgacttctaa gtaaaaccac agcagttgaa 3481 aagactccaa agaaatgtaa gggaaactgc cagcaacgca ggcccccagg tgccagttat 3541 ggctataggt gctacaaaaa cacagcaagg gtgatgggaa agcattgtaa atgtgctttt 3601 aaaaaaaaat actgatgttc ctagtgaaag aggcagcttg aaactgagat gtgaacacat 3661 cagcttgccc tgttaaaaga tgaaaatatt tgtatcacaa atcttaactt gaaggagtcc 3721 ttgcatcaat ttttcttatt tcatttcttt gagtgtctta attaaaagaa tattttaact 3781 tccttggact cattttaaaa aatggaacat aaaatacaat gttatgtatt attattccca 3841 ttctacatac tatggaattt ctcccagtca tttaataaat gtgccttcat tttttcagaa 3901 aaaaaaaaaa aaa

One example of a nucleic acid sequence for human DTX4 is available as NCBI accession number NM_(—)015177 (gi: 148237497). This sequence is recited below for easy reference as SEQ ID NO:133.

1 gagcagcggc agcagcagcg gaccccggcg gcggcggcgg cgcgcggtcc cagccaggcg 61 gccccggtgt cccggccccg gtggatgcac ggctggggag gagcccatgg gccggagctg 121 aggctgcccg gggcggcggg gcgcggggca gggggcgcgg tcgaggcccg gaggcggcgg 181 cgcaggagga agcggaggag gtcgggcgct cggggcccgg gaggcgggcc gcgcagcgcc 241 gcagccccgg gctcgccatg ctcctggcct cggccgtggt ggtctgggaa tggctgaacg 301 agcacggccg ctggcgtccc tacagcccag cggtgagcca ccacatcgag gcggtggtcc 361 gcgccggccc ccgcgcgggg ggcagcgtgg tgctgggcca ggtggacagc cgtctcgcgc 421 cctacatcat cgacctgcag tccatgaacc agttccgcca agacacggga actctccgcc 481 cagttcgccg caactactac gacccctcct cggcccctgg gaagggcgtg gtgtgggagt 541 gggagaacga caatggctcc tggacgccct acgacatgga agtgggcatc accatccagc 601 atgcctatga gaagcagcac ccctggatcg acctcacttc cattggcttt agctacgtaa 661 ttgacttcaa caccatgggc cagatcaacc gtcagaccca gcgccaacgc cgcgtccgcc 721 ggcgcctcga cctcatctac cccatggtca cagggacctt gcctaaggct cagtcctggc 781 cagtcagccc tgggccagcc acctcgcccc ccatgtcccc ctgctcctgt ccccagtgtg 841 tcttggtgat gagtgttaag gcagccgtgg tcaatggcag cactgggccc ctacagctgc 901 cagtgacccg caagaacatg ccgcctcctg gagtggtcaa gctaccccca ctgccaggct 961 ctggggccaa gccactggac agcacaggca ccattcgagg cccactgaag accgccccat 1021 cgcaggtgat ccggagacaa gcctccagca tgcccactgg gacaaccatg ggctctcctg 1081 ccagtccccc aggacccaac agcaagaccg gaagggtggc cctggccacc ttgaatcgta 1141 ccaacctgca gcgactggcc attgcccagt cccgggtgct gatcgcctct ggggtcccca 1201 cagtcccagt gaagaaccta aatgggtcca gtcctgtcaa ccctgccttg gcaggaatca 1261 ctgggatcct catgagtgca gcggggctgc ctgtgtgtct caccaggcca ccaaagctgg 1321 tcctacaccc accccccgtc agcaagagtg aaataaaatc catcccaggg gtttccaaca 1381 caagccgcaa gaccaccaaa aaacaagcca agaaaggtaa aaccccagag gaagtgctaa 1441 aaaaatatct acagaaagtc cggcacccac cagatgagga ctgcaccatc tgtatggaac 1501 gcctcacggc cccctcaggc tacaagggcc cgcagcctac ggtaaaacct gacctggtag 1561 ggaagctgtc cagatgcggc cacgtctacc acatctactg cttggttgcc atgtacaaca 1621 atgggaacaa ggatggaagt ttgcagtgtc caacctgcaa gaccatttat ggggtgaaga 1681 caggcaccca acctccaggg aagatggagt accacctcat cccccactcc ttgcctggcc 1741 acccagactg caaaaccatc cggatcatct acagcatccc ccccggcatt cagggaccgg 1801 aacacccgaa tcctgggaag agtttcagcg cccgaggctt cccacgacac tgttaccttc 1861 cggacagcga gaaagggaga aaagttctga agctgctgct cgtggcctgg gatcgccgcc 1921 tcatttttgc cattggcacc tccagcacca caggcgagtc agacaccgtc atctggaatg 1981 aggtccacca caagacagag tttggctcta atctcactgg ccatggctac ccagatgcca 2041 attacctgga taatgtgctg gctgaactgg ctgcccaggg catctctgag gacagcactg 2101 cccaggagaa ggactgaggc cagaaaagct ttgaggtggg aggggccatg gagactgcag 2161 gacaggaagt gaggagagtg agtcaatgta gaagaagttg gtgtcctgcc ctcccaactt 2221 tctatcctcc cctcctgccc tgtgtccatc cctcatccct cccaaccaca gtgggagcca 2281 gactgaatat agcgacatca ttcataaatc tcatccaaca caaagggaga tgggatgagg 2341 gccatcctgg gtctgttccc atggagtttt tggtgctggg taggcaggaa tcccctccct 2401 accccacctc ccaagtaggg gcatggtcag cacacctagg gtatgggcag tgcttaggca 2461 ctccatatcc tggctttggg aagccggggt ttcttgcctc agccggcttc ttgctacttc 2521 cactctgctt tgagactgga gtttctgcta ttctccctct gctggaggca gggagctctc 2581 actgtgcaag gttggggggt gggcaaaggg gtgaatcact aaactgctgt gacatcagaa 2641 actgatgcct tggtgtagag caaggaagca cttcttccca agagggtcgg agaaggaaaa 2701 gcctctggga gcacattctg ctgtcatcac agtccttggc ttctctgggc cctcctctcc 2761 tcctcacagc tctcacctgt ccaaagaggc atctggttct ctcatgtgga tggatggact 2821 ctggggttcc tctttggagt ggcatcccat gatgctgttt ctagaccctc tctgatcaaa 2881 ccagagcctg catcccactg agcatctgaa ctgtcctcag ggagaggagc ccacagcctt 2941 cttcccaact cattctagac cagctcaaag attccatgag tttcatcgag tcactgtgag 3001 tggagcccat gctgggctct gtgccctctg tgtctgtgca tgcgcgtgtg tgtgtgggcg 3061 tgtgtgcatt gctgggccag cttgaaggga aggcccgtca tgtccctgca ctctgttttg 3121 caagatgcca aaccccagtt ctgatggggc tccaacagcc aggctgtggt cctttgacgt 3181 tcctcacctg ttgccaacct atcccgtagt gaactgaaac cccaatgaag acagaactgt 3241 gcctggggag atgcaatgag gtgagggctg aactcatcct tttatatttc ttttcaagat 3301 tggatcagag ctcatctcca tccagtcttg tttctatgaa ggcttcaatc tgtttccatg 3361 caaatttgct aatcagagcc cagagctgct gggtccctca tctccctcat ctattataga 3421 ttgacttaca gcagggagag aatctcttta gctcattcct aatggagttg ggatcacaat 3481 atggtctggt ccaatctgca tcttgttgtg tcccaagacc ctatctcctc cccaacattc 3541 ttattgcctt tggctcccag taaggaacga attgggggcc agggaggaga acagggggga 3601 tcaagaaggg aaacccaatt ccccctttga aagtgggttc tttgaactat gtgtttgggg 3661 gaagttcctc tggatactaa tttgaattta tatacctcat gttttggggg tttgacgtat 3721 atatatatat atatatatgc atatatattt cataatattt ggaaggtttt tgatgctaga 3781 aaaatggaaa caagagaacc ttcaaaaatg gtacttagat gggaactgga ggccaatctt 3841 tcataaagcc agccccatag ctgcttgctg ttaggcctcc agccattttg acattggggt 3901 ggatagtcga ttcacctgcc tgtcagtcga ttcacctgcc tgtcacccag ttctgtggat 3961 gtgctggtgc tgagcctttg ctctctttcc aaatggttac agggatgttg atcagctcca 4021 ccagagggag ctctgatggg aggaattgct ctgccatcct tgtccctgtg tctcctgtcg 4081 gcaggcagcc attgtatctc accagcagac caggagactg gtcccaaggt tactgcacca 4141 cagggcaatt tcctgccata gttaggaagg aaacacctga actaaatgga agagacatcc 4201 ctgcggtgtt taatatcaca cccatgccct ttgtcaggtt accatgtaca gagattactt 4261 ggagagcctc atgccgtctc taccttcgca cactggtcaa gtatctgctg agcttcttgg 4321 ccgcaaggat gcagaaatag gctgagggtc catgggaaga aagacacaat gaggcagtag 4381 gaggtgggga agaaaagaag acagactttc aaaatggaat taggcactgg ggagagatca 4441 gtttccccac atcagggaga agaaggtata ggtggggaag ggggtggcca ggagcagaag 4501 gaagaagact caagatggaa agggagccgc tgtgcctgtg gcaataccac ttggagaggt 4561 cgacttcata ccttcaagcc ttttcccctg ggcttttgat tgtgtctgtg ccccctttct 4621 tgtcctctct gcagatgccc agtaggggct acctcatcct cgtgctgttc ttgtgtggct 4681 ttctgggcag tagggatctt gaatttcctt tctaacactg tgcccggcaa ggcggggagc 4741 attcctctgc cctttgtctt gtgccaacct ggaaaggtgc agtctagatt tcagtgagaa 4801 ccctgccagc tgagccctgt gcatctacta ccttgacaca gagtgttttc ccactagaag 4861 ctctgctctg ctctcctggc ccaagtaggg gattccatgc cttccctttc atggtcttag 4921 caccagcagc ctagtttctc ccttccagag tctccaggga tgacaaattg gattggagac 4981 aaacctcgtc agatgctcat cccctaaaag gttaattgtg tatttgtggc tgcgtgtgcc 5041 tttgtgtttt cattctcttc ccatttttgt acattttggt cttctctgtg gttttatact 5101 tggtcaaaag tactcgtctt ggtattgcac tgttgtgtgc atgagaaaac tgggggaagg 5161 ctcactggta caagaaagga cccctgaccc ctttccttct ctgtggtccc cggcattaga 5221 ttgggggttc tgggagaggc aggtgaatgt cctaagtgaa ttgttctgtt tgtaactgga 5281 atgtttttga agtctttggt gttgctccgt gaaaggacat cgccacctgg tgctcatgag 5341 gtgtctttgc agaacaataa atggcaaatg aacaaccaca aaattgttac tcttgttggc 5401 cttctgctgt ttgtagatta gtgcacctat ctgtgaggga tttgggttac ctccctgagt 5461 ctgtaagcaa ccacaagccc tgccactggg tgggggaagt ccctccccaa ccacttaaaa 5521 acaaattttc cacatattac ccacccacac atttgacctg gctagacttt gtttgcctaa 5581 aggaacagac cacattgctg ggaaaatgag taagtgaacg tgtgggagaa aaacactttt 5641 agaatcacga atattcactt ttaaaggtct ctttgcctgg ctgcaatata gtgtgtgttt 5701 aaattattta caggctgttg tttctcaaat aaatgtttaa tattaatcat tcccaaactg 5761 acaagaacac aaaaataaaa tgcaaataca gagcc

One example of a nucleic acid sequence for human DUSP4 is available as NCBI accession number NM_(—)001394 (gi: 58331238). This sequence is recited below for easy reference as SEQ ID NO:134.

1 gctgagcgcc ggaggagcgt aggcagggca gcgctggcgc cagtggcgac aggagccgcg 61 cgaccggcaa aaatacacgg gaggccgtcg ccgaaaagag tccgcggtcc tctctcgtaa 121 acacactctc ctccaccggc gcctccccct ccgctctgcg cgccgcccgg ctgggcgccc 181 gaggccgctc cgactgctat gtgaccgcga ggctgcggga ggaaggggac agggaagaag 241 aggctctccc gcgggagccc ttgaggacca agtttgcggc cacttctgca ggcgtccctt 301 cttagctctc gcccgcccct ttctgcagcc taggcggccc gggttctctt ctcttcctcg 361 cgcgcccagc cgcctcggtt cccggcgacc atggtgacga tggaggagct gcgggagatg 421 gactgcagtg tgctcaaaag gctgatgaac cgggacgaga atggcggcgg cgcgggcggc 481 agcggcagcc acggcaccct ggggctgccg agcggcggca agtgcctgct gctggactgc 541 agaccgttcc tggcgcacag cgcgggctac atcctaggtt cggtcaacgt gcgctgtaac 601 accatcgtgc ggcggcgggc taagggctcc gtgagcctgg agcagatcct gcccgccgag 661 gaggaggtac gcgcccgctt gcgctccggc ctctactcgg cggtcatcgt ctacgacgag 721 cgcagcccgc gcgccgagag cctccgcgag gacagcaccg tgtcgctggt ggtgcaggcg 781 ctgcgccgca acgccgagcg caccgacatc tgcctgctca aaggcggcta tgagaggttt 841 tcctccgagt acccagaatt ctgttctaaa accaaggccc tggcagccat cccacccccg 901 gttcccccca gtgccacaga gcccttggac ctgggctgca gctcctgtgg gaccccacta 961 cacgaccagg ggggtcctgt ggagatcctt cccttcctct acctcggcag tgcctaccat 1021 gctgcccgga gagacatgct ggacgccctg ggcatcacgg ctctgttgaa tgtctcctcg 1081 gactgcccaa accactttga aggacactat cagtacaagt gcatcccagt ggaagataac 1141 cacaaggccg acatcagctc ctggttcatg gaagccatag agtacatcga tgccgtgaag 1201 gactgccgtg ggcgcgtgct ggtgcactgc caggcgggca tctcgcggtc ggccaccatc 1261 tgcctggcct acctgatgat gaagaaacgg gtgaggctgg aggaggcctt cgagttcgtt 1321 aagcagcgcc gcagcatcat ctcgcccaac ttcagcttca tggggcagct gctgcagttc 1381 gagtcccagg tgctggccac gtcctgtgct gcggaggctg ctagcccctc gggacccctg 1441 cgggagcggg gcaagacccc cgccaccccc acctcgcagt tcgtcttcag ctttccggtc 1501 tccgtgggcg tgcactcggc ccccagcagc ctgccctacc tgcacagccc catcaccacc 1561 tctcccagct gttagagccg ccctgggggc cccagaacca gagctggctc ccagcaaggg 1621 taggacgggc cgcatgcggg cagaaagttg ggactgagca gctgggagca ggcgaccgag 1681 ctccttcccc atcatttctc cttggccaac gacgaggcca gccagaatgg caataaggac 1741 tccgaataca taataaaagc aaacagaaca ctccaactta gagcaataac ggctgccgca 1801 gcagccaggg aagaccttgg tttggtttat gtgtcagttt cacttttccg atagaaattt 1861 cttacctcat ttttttaagc agtaaggctt gaagtgatga aacccacaga tcctagcaaa 1921 tgtgcccaac cagctttact aaagggggag gaagggaggg caaagggatg agaagacaag 1981 tttcccagaa gtgcctggtt ctgtgtactt gtccctttgt tgtcgttgtt gtagttaaag 2041 gaatttcatt ttttaaaaga aatcttcgaa ggtgtggttt tcatttctca gtcaccaaca 2101 gatgaataat tatgcttaat aataaagtat ttattaagac tttcttcaga gtatgaaagt 2161 acaaaaagtc tagttacagt ggatttagaa tatatttatg ttgatgtcaa acagctgagc 2221 accgtagcat gcagatgtca aggcagttag gaagtaaatg gtgtcttgta gatatgtgca 2281 aggtagcatg atgagcaact tgagtttgtt gccactgaga agcaggcggg ttgggtggga 2341 ggaggaagaa agggaagaat taggtttgaa ttgcttttta aaaaaaaaag aaaagaaaaa 2401 gacagcatct cactatgttg ccaaggctca tcttgagaag caggcgggtt gggtgggagg 2461 aggaagaaag ggaagaatta ggtttgaatt gctttttt

One example of a nucleic acid sequence for human EFEMP1 is available as NCBI accession number NM_(—)004105 (gi: 86787911). This sequence is recited below for easy reference as SEQ ID NO:135.

1 cgaaggtagc gtgtcgggga cccagactga taagacaaaa gagaatcagt cgctttgggc 61 tgcccctcca cacaacctgg gacttttaaa caaagctgtg cgcagagaaa ggcgtggaaa 121 tgccactttg agagtttgtg ctgggggatg tgagaagctc tgagacatgt gagaaggtct 181 agtattctac tagaactgga agattgctct ccgagttttg ttttgttatt ttgtttaaaa 241 aataaaaagc ttgaggccaa ggcaattcat attggctcac aggtattttt gctgtgctgt 301 gcaaggaact ctgctagctc aagattcaca atgttgaaag cccttttcct aactatgctg 361 actctggcgc tggtcaagtc acaggacacc gaagaaacca tcacgtacac gcaatgcact 421 gacggatatg agtgggatcc tgtgagacag caatgcaaag atattgatga atgtgacatt 481 gtcccagacg cttgtaaagg tggaatgaag tgtgtcaacc actatggagg atacctctgc 541 cttccgaaaa cagcccagat tattgtcaat aatgaacagc ctcagcagga aacacaacca 601 gcagaaggaa cctcaggggc aaccaccggg gttgtagctg ccagcagcat ggcaaccagt 661 ggagtgttgc ccgggggtgg ttttgtggcc agtgctgctg cagtcgcagg ccctgaaatg 721 cagactggcc gaaataactt tgtcatccgg cggaacccag ctgaccctca gcgcattccc 781 tccaaccctt cccaccgtat ccagtgtgca gcaggctacg agcaaagtga acacaacgtg 841 tgccaagaca tagacgagtg cactgcaggg acgcacaact gtagagcaga ccaagtgtgc 901 atcaatttac ggggatcctt tgcatgtcag tgccctcctg gatatcagaa gcgaggggag 961 cagtgcgtag acatagatga atgtaccatc cctccatatt gccaccaaag atgcgtgaat 1021 acaccaggct cattttattg ccagtgcagt cctgggtttc aattggcagc aaacaactat 1081 acctgcgtag atataaatga atgtgatgcc agcaatcaat gtgctcagca gtgctacaac 1141 attcttggtt cattcatctg tcagtgcaat caaggatatg agctaagcag tgacaggctc 1201 aactgtgaag acattgatga atgcagaacc tcaagctacc tgtgtcaata tcaatgtgtc 1261 aatgaacctg ggaaattctc atgtatgtgc ccccagggat accaagtggt gagaagtaga 1321 acatgtcaag atataaatga gtgtgagacc acaaatgaat gccgggagga tgaaatgtgt 1381 tggaattatc atggcggctt ccgttgttat ccacgaaatc cttgtcaaga tccctacatt 1441 ctaacaccag agaaccgatg tgtttgccca gtctcaaatg ccatgtgccg agaactgccc 1501 cagtcaatag tctacaaata catgagcatc cgatctgata ggtctgtgcc atcagacatc 1561 ttccagatac aggccacaac tatttatgcc aacaccatca atacttttcg gattaaatct 1621 ggaaatgaaa atggagagtt ctacctacga caaacaagtc ctgtaagtgc aatgcttgtg 1681 ctcgtgaagt cattatcagg accaagagaa catatcgtgg acctggagat gctgacagtc 1741 agcagtatag ggaccttccg cacaagctct gtgttaagat tgacaataat agtggggcca 1801 ttttcatttt agtcttttct aagagtcaac cacaggcatt taagtcagcc aaagaatatt 1861 gttaccttaa agcactattt tatttataga tatatctagt gcatctacat ctctatactg 1921 tacactcacc cataattcaa acaattacac catggtataa agtgggcatt taatatgtaa 1981 agattcaaag tttgtcttta ttactatatg taaattagac attaatccac taaactggtc 2041 ttcttcaaga gagctaagta tacactatct ggtgaaactt ggattctttc ctataaaagt 2101 gggaccaagc aatgatgatc ttctgtggtg cttaaggaaa cttactagag ctccactaac 2161 agtctcataa ggaggcagcc atcataacca ttgaatagca tgcaagggta agaatgagtt 2221 tttaactgct ttgtaagaaa atggaaaagg tcaataaaga tatatttctt tagaaaatgg 2281 ggatctgcca tatttgtgtt ggtttttatt ttcatatcca gcctaaaggt ggttgtttat 2341 tatatagtaa taaatcattg ctgtacaata tgctggtttc tgtagggtat ttttaatttt 2401 gtcagaaatt ttagattgtg aatattttgt aaaaaacagt aagcaaaatt ttccagaatt 2461 cccaaaatga accagatatc ccctagaaaa ttatactatt gagaaatcta tggggaggat 2521 atgagaaaat aaattccttc taaaccacat tggaactgac ctgaagaagc aaactcggaa 2581 aatataataa catccctgaa ttcaggactt ccacaagatg cagaacaaaa tggataaaag 2641 gtatttcact ggagaagttt taatttctaa gtaaaattta aatcctaaca cttcactaat 2701 ttataactaa aatttctcat cttcgtactt gatgctcaca gaggaagaaa atgatgatgg 2761 tttttattcc tggcatccag agtgacagtg aacttaagca aattaccctc ctacccaatt 2821 ctatggaata ttttatacgt ctccttgttt aaaatgtcac tgctttactt tgatgtatca 2881 tatttttaaa taaaaataaa tattccttta gaagatcaaa aaaaaaaaaa aaaaaa

One example of a nucleic acid sequence for human ELMO1 is available as NCBI accession number NM_(—)014800 (gi: 86787650). This sequence is recited below for easy reference as SEQ ID NO:136.

1 aagtgagagc agcggcagcc ggcggtgcag cagccggccg acccagagtg taagtgcgtg 61 tgctggggcg agcgggagcg ggcgaggatg ggcacaggat agaggcagag ccacccacgc 121 cgccgcggcc ccacgctggg cgacagagcc tccagttccc cttcaatggt ggcgggtcgc 181 cggagctctg atcgccggga acccttgccg ctgctgtcct gcgaccccaa gcaggtatag 241 acacgtgtgg ccgtttacgc tgtaggatcc tcattcccac tggctttgaa cattttgggg 301 acttacaatg ccgccacccg cggacatcgt caaggtggcc atagaatggc cgggcgccta 361 ccccaaactc atggaaattg atcagaaaaa accactgtct gcaataataa aggaagtctg 421 tgatgggtgg tctcttgcca accatgaata ttttgcactc cagcatgccg atagttcaaa 481 cttctatatc acagaaaaga accgcaatga gataaaaaat ggcactatcc ttcgattaac 541 cacatctcca gctcagaacg cccagcagct ccatgaacga atccagtcct cgagtatgga 601 tgccaagctg gaagccctga aggacttggc cagcctctcc cgggatgtca cgtttgccca 661 ggagtttata aacctggacg gtatctctct cctcacgcag atggtggaga gcggcactga 721 gcgataccag aaattgcaga agatcatgaa gccttgcttt ggagacatgc tgtccttcac 781 cctgacggcc ttcgttgagc tgatggacca tggcatagtg tcctgggata cattttcggt 841 ggcgttcatt aagaagatag caagttttgt gaacaagtca gccatagaca tctcgatcct 901 gcagcggtcc ttggccattt tggagtcgat ggtgctcaat agccatgacc tctaccagaa 961 agtggcgcag gagatcacca tcggccagct cattccacac ctgcaagggt cagatcaaga 1021 aatccaaacc tatactattg cagtgattaa tgcgcttttc ctgaaggctc ctgatgagag 1081 gaggcaggag atggcgaata ttttggctca gaagcaactg cgttccatca ttttaacaca 1141 tgtcatccga gcccagcggg ccatcaacaa tgagatggcg caccagctgt atgttctaca 1201 agtgctcacc tttaacctcc tggaagacag gatgatgacc aaaatggacc cccaggacca 1261 ggctcagagg gacatcatat ttgaacttcg aagaattgct tttgatgctg agtctgaacc 1321 taacaacagc agtggcagca tggagaaacg caagtccatg tacacgcgag attataagaa 1381 gcttgggttc attaatcatg tcaaccctgc catggacttc acgcagactc cacctgggat 1441 gttggctctg gacaacatgc tgtactttgc caagcaccac caagatgcct acatccggat 1501 tgtgcttgag aacagtagtc gagaagacaa gcatgaatgt ccctttggcc gcagtagtat 1561 agagctgacc aagatgctat gtgagatctt gaaagtgggc gagttgccta gtgagacctg 1621 caacgacttc cacccgatgt tcttcaccca cgacagatcc tttgaggagt ttttctgcat 1681 ctgtatccag ctcctgaaca agacatggaa ggaaatgagg gcaacttctg aagacttcaa 1741 caaggtaatg caggtggtga aggagcaggt tatgagagca cttacaacca agcctagctc 1801 cctggaccag ttcaagagca aactgcagaa cctgagctac actgagatcc tgaaaatccg 1861 ccagtccgag aggatgaacc aggaagattt ccagtcccgc ccgattttgg aactaaagga 1921 gaagattcag ccagaaatct tagagctgat caaacagcaa cgcctgaacc gccttgtgga 1981 agggacctgc tttaggaaac tcaatgcccg gcggaggcaa gacaagtttt ggtattgtcg 2041 gctttcgcca aatcacaaag tcctgcatta cggagactta gaagagagtc ctcagggaga 2101 agtgccccac gattccttgc aggacaaact gccggtggca gatatcaaag ccgtggtgac 2161 gggaaaggac tgccctcata tgaaagagaa aggtgccctt aaacaaaaca aggaggtgct 2221 tgaactcgct ttctccatct tgtatgactc aaactgccaa ctgaacttca tcgctcctga 2281 caagcatgag tactgtatct ggacggatgg actgaatgcg ctactcggga aggacatgat 2341 gagcgacctg acgcggaatg acctggacac cctgctcagc atggaaatca agctccgcct 2401 cctggacctg gaaaacatcc agatccctga cgcacctccg ccgattccca aggagcccag 2461 caactatgac ttcgtctatg actgtaactg aagtggccgg gcccagacat gccccttcca 2521 aaactggaac acctagctaa caggagagag gaatgaaaac acacccacgc cttggaaccg 2581 tcctttggta aagggaagct gtgggtccac attcccttca gcatcacctc tagccctggc 2641 aactttcagc ccctagctgg catcttgctc accgccctga ttctgttcct cggctccact 2701 gcttcaggtc acttcccatg gctgcagtcc actggtggga caagagcaaa gcccactgcc 2761 agtaagaagg ccaaagggcc cttccatcct agccctctgc aggcatgccc ttccttccct 2821 tgggcaggaa agccagcagc cccagactgc ccaaaaactt gcccaccaga ccaagggcag 2881 tgccccaagg cccctgtctg gaggaaatgg cctagctatt tgatgagaag accaaacccc 2941 acatcctcct ttcccctctc tctagaatca tctcgcacca ccagttacac ttgaattaag 3001 atctgcgctc aaatctcctc ccacctctct ccctgctttt gccttgctct gttcctcttt 3061 ggtcccaaga gcagcagccg cagcctcctc gtgatcctcc ctagcataaa tttcccaaac 3121 agtccacagg tcccatgccc actttgcgtc tgcactgtga tcgtgacaaa tcttccctcc 3181 tcaccagcta gtctggggtt tcctctccct gccccaggcc agaactgcct tcttcatttc 3241 cacccacgct cccagcctct tagctgaaag cacaaatggt gaaatcagta gtctcgctcc 3301 atctctaata gactaaacct aaatgcctct aggacggact gttgctatcc aagcgtttgg 3361 tgttaccttc tcctgggagg tcctgctgca actcaagttc cacaggatgg tcaagctgtc 3421 agacatccaa gtttacatca ttgtaattat tactggtatt tacaatttgc aagagttttg 3481 ggttagtttt tttttttttt tttgctttgt ttttgtacaa aagagtctaa cattttttgc 3541 caaacagata tatatttaat gaaaagaaga gatacataaa tgtgtgaatt tccagttttt 3601 ttttaattat tttaatccca aacatcttcc tgaaaataac attcccttaa acatgctgtg 3661 gaataaaatg gattgtgatg atttggaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3721 aaaaaaa

One example of a nucleic acid sequence for human FGFR2 is available as NCBI accession number NM_(—)000141 (gi: 189083823). This sequence is recited below for easy reference as SEQ ID NO:137.

1 ggcggcggct ggaggagagc gcggtggaga gccgagcggg cgggcggcgg gtgcggagcg 61 ggcgagggag cgcgcgcggc cgccacaaag ctcgggcgcc gcggggctgc atgcggcgta 121 cctggcccgg cgcggcgact gctctccggg ctggcggggg ccggccgcga gccccggggg 181 ccccgaggcc gcagcttgcc tgcgcgctct gagccttcgc aactcgcgag caaagtttgg 241 tggaggcaac gccaagcctg agtcctttct tcctctcgtt ccccaaatcc gagggcagcc 301 cgcgggcgtc atgcccgcgc tcctccgcag cctggggtac gcgtgaagcc cgggaggctt 361 ggcgccggcg aagacccaag gaccactctt ctgcgtttgg agttgctccc cgcaaccccg 421 ggctcgtcgc tttctccatc ccgacccacg cggggcgcgg ggacaacaca ggtcgcggag 481 gagcgttgcc attcaagtga ctgcagcagc agcggcagcg cctcggttcc tgagcccacc 541 gcaggctgaa ggcattgcgc gtagtccatg cccgtagagg aagtgtgcag atgggattaa 601 cgtccacatg gagatatgga agaggaccgg ggattggtac cgtaaccatg gtcagctggg 661 gtcgtttcat ctgcctggtc gtggtcacca tggcaacctt gtccctggcc cggccctcct 721 tcagtttagt tgaggatacc acattagagc cagaagagcc accaaccaaa taccaaatct 781 ctcaaccaga agtgtacgtg gctgcgccag gggagtcgct agaggtgcgc tgcctgttga 841 aagatgccgc cgtgatcagt tggactaagg atggggtgca cttggggccc aacaatagga 901 cagtgcttat tggggagtac ttgcagataa agggcgccac gcctagagac tccggcctct 961 atgcttgtac tgccagtagg actgtagaca gtgaaacttg gtacttcatg gtgaatgtca 1021 cagatgccat ctcatccgga gatgatgagg atgacaccga tggtgcggaa gattttgtca 1081 gtgagaacag taacaacaag agagcaccat actggaccaa cacagaaaag atggaaaagc 1141 ggctccatgc tgtgcctgcg gccaacactg tcaagtttcg ctgcccagcc ggggggaacc 1201 caatgccaac catgcggtgg ctgaaaaacg ggaaggagtt taagcaggag catcgcattg 1261 gaggctacaa ggtacgaaac cagcactgga gcctcattat ggaaagtgtg gtcccatctg 1321 acaagggaaa ttatacctgt gtagtggaga atgaatacgg gtccatcaat cacacgtacc 1381 acctggatgt tgtggagcga tcgcctcacc ggcccatcct ccaagccgga ctgccggcaa 1441 atgcctccac agtggtcgga ggagacgtag agtttgtctg caaggtttac agtgatgccc 1501 agccccacat ccagtggatc aagcacgtgg aaaagaacgg cagtaaatac gggcccgacg 1561 ggctgcccta cctcaaggtt ctcaaggccg ccggtgttaa caccacggac aaagagattg 1621 aggttctcta tattcggaat gtaacttttg aggacgctgg ggaatatacg tgcttggcgg 1681 gtaattctat tgggatatcc tttcactctg catggttgac agttctgcca gcgcctggaa 1741 gagaaaagga gattacagct tccccagact acctggagat agccatttac tgcatagggg 1801 tcttcttaat cgcctgtatg gtggtaacag tcatcctgtg ccgaatgaag aacacgacca 1861 agaagccaga cttcagcagc cagccggctg tgcacaagct gaccaaacgt atccccctgc 1921 ggagacaggt aacagtttcg gctgagtcca gctcctccat gaactccaac accccgctgg 1981 tgaggataac aacacgcctc tcttcaacgg cagacacccc catgctggca ggggtctccg 2041 agtatgaact tccagaggac ccaaaatggg agtttccaag agataagctg acactgggca 2101 agcccctggg agaaggttgc tttgggcaag tggtcatggc ggaagcagtg ggaattgaca 2161 aagacaagcc caaggaggcg gtcaccgtgg ccgtgaagat gttgaaagat gatgccacag 2221 agaaagacct ttctgatctg gtgtcagaga tggagatgat gaagatgatt gggaaacaca 2281 agaatatcat aaatcttctt ggagcctgca cacaggatgg gcctctctat gtcatagttg 2341 agtatgcctc taaaggcaac ctccgagaat acctccgagc ccggaggcca cccgggatgg 2401 agtactccta tgacattaac cgtgttcctg aggagcagat gaccttcaag gacttggtgt 2461 catgcaccta ccagctggcc agaggcatgg agtacttggc ttcccaaaaa tgtattcatc 2521 gagatttagc agccagaaat gttttggtaa cagaaaacaa tgtgatgaaa atagcagact 2581 ttggactcgc cagagatatc aacaatatag actattacaa aaagaccacc aatgggcggc 2641 ttccagtcaa gtggatggct ccagaagccc tgtttgatag agtatacact catcagagtg 2701 atgtctggtc cttcggggtg ttaatgtggg agatcttcac tttagggggc tcgccctacc 2761 cagggattcc cgtggaggaa ctttttaagc tgctgaagga aggacacaga atggataagc 2821 cagccaactg caccaacgaa ctgtacatga tgatgaggga ctgttggcat gcagtgccct 2881 cccagagacc aacgttcaag cagttggtag aagacttgga tcgaattctc actctcacaa 2941 ccaatgagga atacttggac ctcagccaac ctctcgaaca gtattcacct agttaccctg 3001 acacaagaag ttcttgttct tcaggagatg attctgtttt ttctccagac cccatgcctt 3061 acgaaccatg ccttcctcag tatccacaca taaacggcag tgttaaaaca tgaatgactg 3121 tgtctgcctg tccccaaaca ggacagcact gggaacctag ctacactgag cagggagacc 3181 atgcctccca gagcttgttg tctccacttg tatatatgga tcagaggagt aaataattgg 3241 aaaagtaatc agcatatgtg taaagattta tacagttgaa aacttgtaat cttccccagg 3301 aggagaagaa ggtttctgga gcagtggact gccacaagcc accatgtaac ccctctcacc 3361 tgccgtgcgt actggctgtg gaccagtagg actcaaggtg gacgtgcgtt ctgccttcct 3421 tgttaatttt gtaataattg gagaagattt atgtcagcac acacttacag agcacaaatg 3481 cagtatatag gtgctggatg tatgtaaata tattcaaatt atgtataaat atatattata 3541 tatttacaag gagttatttt ttgtattgat tttaaatgga tgtcccaatg cacctagaaa 3601 attggtctct ctttttttaa tagctatttg ctaaatgctg ttcttacaca taatttctta 3661 attttcaccg agcagaggtg gaaaaatact tttgctttca gggaaaatgg tataacgtta 3721 atttattaat aaattggtaa tatacaaaac aattaatcat ttatagtttt ttttgtaatt 3781 taagtggcat ttctatgcag gcagcacagc agactagtta atctattgct tggacttaac 3841 tagttatcag atcctttgaa aagagaatat ttacaatata tgactaattt ggggaaaatg 3901 aagttttgat ttatttgtgt ttaaatgctg ctgtcagacg attgttctta gacctcctaa 3961 atgccccata ttaaaagaac tcattcatag gaaggtgttt cattttggtg tgcaaccctg 4021 tcattacgtc aacgcaacgt ctaactggac ttcccaagat aaatggtacc agcgtcctct 4081 taaaagatgc cttaatccat tccttgagga cagaccttag ttgaaatgat agcagaatgt 4141 gcttctctct ggcagctggc cttctgcttc tgagttgcac attaatcaga ttagcctgta 4201 ttctcttcag tgaattttga taatggcttc cagactcttt ggcgttggag acgcctgtta 4261 ggatcttcaa gtcccatcat agaaaattga aacacagagt tgttctgctg atagttttgg 4321 ggatacgtcc atctttttaa gggattgctt tcatctaatt ctggcaggac ctcaccaaaa 4381 gatccagcct catacctaca tcagacaaaa tatcgccgtt gttccttctg tactaaagta 4441 ttgtgttttg ctttggaaac acccactcac tttgcaatag ccgtgcaaga tgaatgcaga 4501 ttacactgat cttatgtgtt acaaaattgg agaaagtatt taataaaacc tgttaatttt 4561 tatactgaca ataaaaatgt ttctacagat attaatgtta acaagacaaa ataaatgtca 4621 cgcaacttat ttttttaata aaaaaaaaaa aaaa

One example of a nucleic acid sequence for human FLRT1 is available as NCBI accession number NM_(—)013280 (gi: 48762940). This sequence is recited below for easy reference as SEQ ID NO:138.

1 caaggaggct gctgattgtg gcccacagcc tcatctgaac gccaggagac caggataccg 61 aggcaccgga tcccctctct gtgccctggg gagccccagt gctgcccagt caccccaggg 121 ctgaggtctg cgtccctagt ggtgcaaggc ctggtaggac cacggggcag ggaatgtgag 181 cgccatctga gctcacggtg tcctgagtcg cggcttcgtg actttggcag gggcctccgg 241 accagtgacc ccagtcaaac ccagagggtc ttgggcggca gcgacgaagg aggtattcag 301 gctccaggcc aggtggggcc ggacgccccc agccatccac catggtggtg gcacacccca 361 ccgccactgc caccaccacg cccactgcca ctgtcacggc caccgttgtg atgaccacgg 421 ccaccatgga cctgcgggac tggctgttcc tctgctacgg gctcatcgcc ttcctgacgg 481 aggtcatcga cagcaccacc tgcccctcgg tgtgccgctg cgacaacggc ttcatctact 541 gcaacgaccg gggactcaca tccatccccg cagatatccc tgatgatgcc accaccctct 601 acctgcagaa caaccagatc aacaacgccg gcatccccca ggacctcaag accaaggtca 661 acgtgcaggt catctaccta tacgagaatg acctggatga gttccccatc aacctgcccc 721 gctccctccg ggagctgcac ctgcaggaca acaatgtgcg caccattgcc agggactcgc 781 tggcccgcat cccgctgctg gagaagctgc acctggatga caactccgtg tccaccgtca 841 gcattgagga ggacgccttc gccgacagca aacagctcaa gctgctcttc ctgagccgga 901 accacctgag cagcatcccc tcggggctgc cgcacacgct ggaggagctg cggctggatg 961 acaaccgcat ctccaccatc ccgctgcatg ccttcaaggg cctcaacagc ctgcggcgcc 1021 tggtgctgga cggtaacctg ctggccaacc agcgcatcgc cgacgacacc ttcagccgcc 1081 tacagaacct cacagagctc tcgctggtgc gcaattcgct ggccgcgcca cccctcaacc 1141 tgcccagcgc ccacctgcag aagctctacc tgcaggacaa tgccatcagc cacatcccct 1201 acaacacgct ggccaagatg cgtgagctgg agcggctgga cctgtccaac aacaacctga 1261 ccacgctgcc ccgcggcctg ttcgacgacc tggggaacct ggcccagctg ctgctcagga 1321 acaacccttg gttttgtggc tgcaacctca tgtggctgcg ggactgggtg aaggcacggg 1381 cggccgtggt caacgtgcgg ggcctcatgt gccagggccc tgagaaggtc cggggcatgg 1441 ccatcaagga cattaccagc gagatggacg agtgttttga gacggggccg cagggcggcg 1501 tggccaatgc ggctgccaag accacggcca gcaaccacgc ctctgccacc acgccccagg 1561 gttccctgtt taccctcaag gccaaaaggc cagggctgcg cctccccgac tccaacattg 1621 actaccccat ggccacgggt gatggcgcca agaccctggc catccacgtg aaggccctga 1681 cggcagactc catccgcatc acgtggaagg ccacgctccc cgcctcctct ttccggctca 1741 gttggctgcg cctgggccac agcccagccg tgggctccat cacggagacc ttggtgcagg 1801 gggacaagac agagtacctg ctgacagccc tggagcccaa gtccacctac atcatctgca 1861 tggtcaccat ggagaccagc aatgcctacg tagctgatga gacacccgtg tgtgccaagg 1921 cagagacagc cgacagctat ggccctacca ccacactcaa ccaggagcag aacgctggcc 1981 ccatggcgag cctgcccctg gcgggcatca tcggcggggc agtggctctg gtcttcctct 2041 tcctggtcct gggggccatc tgctggtacg tgcaccaggc tggcgagctg ctgacccggg 2101 agagggccta caaccggggc agcaggaaaa aggatgacta tatggagtca gggaccaaga 2161 aggataactc catcctggaa atccgcggcc ctgggctgca gatgctgccc atcaacccgt 2221 accgcgccaa agaggagtac gtggtccaca ctatcttccc ctccaacggc agcagcctct 2281 gcaaggccac acacaccatt ggctacggca ccacgcgggg ctaccgggac ggcggcatcc 2341 ccgacataga ctactcctac acatgatgcc cgcccacccg ggctgccccg cctcagcccc 2401 agctgccctg gcgtggccat gtggctttgc ccagcctgct gcaatccaag agagcaagga 2461 agagaaattc catgggtgac tttcctccgc agaaagcaaa gtttggggag ggctgacgat 2521 tttgtagaac acaacagtga caattttttt taaaagaata gaaggcagga gggggaattc 2581 gacattgttg aagacataat ttataccaag ttatgccagt tggggaggga aggactaaaa 2641 ataatattgc aggcagggct gggttgggtt tttttttttt cccccctgaa ctggaaggat 2701 actacctgta caacatctgt ggacacctca tgctctgttc aaggccatca caaaggaacc 2761 gccagggaga agcagccggc tctcaaagct cccacgcagc tctcccgcca ctggccactc 2821 gctggcgacc cgatggaagg ttttcaggct cctcacaaag gagagaggga agaaaagatc 2881 ttttgccctg gagatatggt cctgaaatct ctcccctggc ttattccata ccatttccct 2941 tgcagatttg cagaaacatg gcatctttca ctgcattctt tgaacaatca tgtagtcgat 3001 taaaaaaaaa aaacaaactt ttttttccta ggctgaagcc ctcttcagtt ccatgcacca 3061 cgctccgtag aagccccggc ggaagccgta gctttccctg ccacctggag gtgcatctgt 3121 ctgcctgtct atccctgtcg cggtgtctct aagtacagat gggtagatag agccacatgc 3181 acggtcctta ccgttcttct tgggtcagtt cttaccattt cctgaacaat agaattgtga 3241 aagtgttaaa aa

One example of a nucleic acid sequence for human FMOD is available as NCBI accession number NM_(—)002023 (gi: 71040110). This sequence is recited below for easy reference as SEQ ID NO:139.

1 ggtctggcac aggcacgcac actctcagta gactctttca ctcctctctc tcttcctctc 61 tcacacgttc tccaacccaa ggaggccaga cagagggacg tggtcactct ctgaaaagtt 121 caacttgaga gacaaaatgc agtggacctc cctcctgctg ctggcagggc tcttctccct 181 ctcccaggcc cagtatgaag atgaccctca ttggtggttc cactacctcc gcagccagca 241 gtccacctac tacgatccct atgaccctta cccgtatgag acctacgagc cttaccccta 301 tggggtggat gaagggccag cctacaccta cggctctcca tcccctccag atccccgcga 361 ctgcccccag gagtgcgact gcccacccaa cttccccacg gccatgtact gtgacaatcg 421 caacctcaag tacctgccct tcgttccctc ccgcatgaag tatgtgtact tccagaacaa 481 ccagatcacc tccatccagg aaggcgtctt tgacaatgcc acagggctgc tctggattgc 541 tctccacggc aaccagatca ccagtgataa ggtgggcagg aaggtcttct ccaagctgag 601 gcacctggag aggctgtacc tggaccacaa caacctgacc cggatgcccg gtcccctgcc 661 tcgatccctg agagagctcc atctcgacca caaccagatc tcacgggtcc ccaacaatgc 721 tctggagggg ctggagaacc tcacggcctt gtacctccaa cacaatgaga tccaggaagt 781 gggcagttcc atgaggggcc tccggtcact gatcttgctg gacctgagtt ataaccacct 841 tcggaaggtg cctgatgggc tgccctcagc tcttgagcag ctgtacatgg agcacaacaa 901 tgtctacacc gtccccgata gctacttccg gggggcgccc aagctgctgt atgtgcggct 961 gtcccacaac agtctaacca acaatggcct ggcctccaac accttcaatt ccagcagcct 1021 ccttgagcta gacctctcct acaaccagct gcagaagatc cccccagtca acaccaacct 1081 ggagaacctc tacctccaag gcaataggat caatgagttc tccatcagca gcttctgcac 1141 cgtggtggac gtcgtgaact tctccaagct gcaggtgctg cgcctggacg ggaacgagat 1201 caagcgcagc gccatgcctg ccgacgcgcc cctctgcctg cgccttgcca gcctcatcga 1261 gatctgagca gccctggcac cgggtactgg gcggagagcc cccgtggcat ttggcttgat 1321 ggtttggttt ggcttttgct ggaaggtcca ggatggacca tgtgacagaa gtccacgggc 1381 accctctgta gtcttctttc ctgtaggtgg ggttaggggg ggcgatcagg gacaggcagc 1441 cttctgctga ggacataggc agaagctcac tcttttccag ggacagaagt ggtggtagat 1501 ggaaggatcc ctggatgttc caaccccata aatctcacgg ctcttaagtt cttcccaatg 1561 atctgaggtc atggaacttc aaaagtggca tgggcaatag tatataacca tacttttcta 1621 acaatccctg gctgtctgtg agcagcactt gacagctctc cctctgtgct gggctggtcg 1681 tgcagttact ctgggctccc atttgttgct tctcaaaata tacctcttgc ccagctgcct 1741 cttctgaaat ccacttcacc cactccactt tcctccacag atgcctcttc tgtgccttaa 1801 gcagagtcag gagaccccaa ggcatgtgag catctgccca gcaacctgtg gagacaaccc 1861 acactgtgtc tgagggtgaa aggacaccag gagtcacttc tatacctccc taacctcacc 1921 cctggaaagc caccagattg gaggtcacca gcatgatgat aatattcatg acctgatgtg 1981 ggaggagaca gccaacctca ggcttagatc aatgtatagg gctatatttt ggcagctggg 2041 tagctctttg aaggtggata agacttcaga agaggaaagg ccagactttg cttaccatca 2101 gcatctgcaa tgggccaaac acacctcaaa ttggctgagt tgagaaagca gccccagtag 2161 ttccattctt gcccagcact ttctgcattc caaacagcat cctacctggg tttttatcca 2221 caaaggtagc ggccacatgg tttttaaagt atgagaaaca cagtttgtcc tctcctttta 2281 tccaagcagg aagattctat atcctgatgg tagagacaga ctccaggcag ccctggactt 2341 gctagcccaa agaaggagga tgtggttaat ctgtttcacc tggtttgtcc taaggccata 2401 gttaaaaagt accagctctg gctggggtcc gtgaagccca ggccaggcag ccaaatcttg 2461 cctgtgctgg gcatacaacc ctctgctttc acatctctga gctatatcct cattagtgaa 2521 ggtggctttt gctttatagt ttggctgggg agcacttaat tcttcccatt tcaaaaggta 2581 atgttgcctg gggcttaacc cacctgccct ttgggcaagg ttgggacaaa gccatctggg 2641 cagtcagggg caaggactgt tggaggagag ttagcccaag tataggctct gcccagatgc 2701 catcacatcc ctgatactgt gtatgctttg aagcaccttc cctgagaagg gaagagggga 2761 tctttggact acgttcttgg ctccagacct ggaatccaca aaagccaaac cagctcattt 2821 caacaaagga gctccgatgt gaggggcaag gctgccccct gccccagggc tcttcagaaa 2881 gcatctgcat gtgaacacca tcatgccttt ataaaggatc cttattacag gaaaagcatg 2941 agtggtggct aacctgacca ataaagttat tttatgattg catctaaaaa aaaaaaaaaa 3001 aaaaa

One example of a nucleic acid sequence for human GALNT7 is available as NCBI accession number NM_(—)017423 (gi: 157502211). This sequence is recited below for easy reference as SEQ ID NO:140.

1 agagccggag gagggggaag gagggagggg agagcggtgg cggcggctgc gccgggctgt 61 gagtctctcg ccgccggagg aagatgaggc tgaagattgg gttcatctta cgcagtttgc 121 tggtggtggg aagcttcctg gggctagtgg tcctctggtc ttccctgacc ccgcggccgg 181 acgacccaag cccgctgagc aggatgaggg aagacagaga tgtcaatgac cccatgccca 241 accgaggcgg caatggacta gctcctgggg aggacagatt caaacctgtg gtaccatggc 301 ctcatgttga aggagtagaa gtggacttag agtctattag aagaataaac aaggccaaaa 361 atgaacaaga gcaccatgct ggaggagatt cccagaaaga tatcatgcag aggcagtatc 421 tcacatttaa gcctcagaca ttcacctacc atgatcctgt gcttcgccca gggatcctcg 481 gtaactttga acccaaagaa cctgagcctc ctggagtggt tggtggccct ggagagaaag 541 ccaagccatt ggttttggga ccagaattca aacaagcaat tcaagccagc attaaagagt 601 ttggatttaa catggtggca agtgacatga tctcactgga ccgcagcgtc aatgacttac 661 gccaagaaga atgcaagtat tggcattatg atgaaaactt gctcacttcg agcgttgtca 721 ttgtcttcca taatgaagga tggtcaaccc tcatgagaac agtccacagt gtaattaaaa 781 ggactccaag gaaatattta gcagaaattg tgttaattga cgatttcagt aataaagaac 841 acttaaaaga aaaactggat gaatatatta agctgtggaa tggcctagtg aaggtatttc 901 gaaatgaaag aagggaaggt ttaattcaag cacgaagtat tggtgctcag aaggctaaac 961 ttggacaggt tttgatatac cttgatgccc actgtgaggt ggcagttaac tggtatgcac 1021 cacttgtagc tcccatatct aaggacagaa ccatttgcac tgtgccgctt atagatgtca 1081 taaatggcaa cacatatgaa attatacccc aagggggtgg tgatgaagat gggtatgccc 1141 gaggagcatg ggattggagt atgctctgga aacgggtgcc tctgacccct caagagaaga 1201 gactgagaaa gacaaaaact gaaccgtatc ggtccccagc catggctggg ggattatttg 1261 ccattgaacg agagttcttc tttgaattgg gtctctatga tccaggtctc cagatttggg 1321 gtggtgaaaa ctttgagatc tcatacaaga tatggcagtg tggtggcaaa ttattatttg 1381 ttccttgttc tcgtgttgga catatctacc gtcttgaggg ctggcaagga aatcctccgc 1441 ccatttatgt tgggtcttct ccaactctga agaattatgt tagagttgtg gaggtttggt 1501 gggatgaata taaagactac ttctatgcta gtcgtcctga atcgcaggca ttaccatatg 1561 gggatatatc ggagctgaaa aaatttcgag aagatcacaa ctgcaaaagt tttaagtggt 1621 tcatggaaga aatagcttat gatatcacct cacactaccc tttgccaccc aaaaatgttg 1681 actggggaga aatcagaggc ttcgaaactg cttactgcat tgatagcatg ggaaaaacaa 1741 atggaggctt tgttgaacta ggaccctgcc acaggatggg agggaatcag cttttcagaa 1801 tcaatgaagc aaatcaactc atgcagtatg accagtgttt gacaaaggga gctgatggat 1861 caaaagttat gattacacac tgtaatctaa atgaatttaa ggaatggcag tacttcaaga 1921 acctgcacag atttactcat attccttcag gaaagtgttt agatcgctca gaggtcctgc 1981 atcaagtatt catctccaat tgtgactcca gtaaaacgac tcaaaaatgg gaaatgaata 2041 acatccatag tgtttagaga gaaaaaaata aaccaataac ctacctactg acaagtaaat 2101 ttatacagga ctgaaaaccg cctgaaacct gctgcaacta ttgttattaa ctctgtatag 2161 ctccaaacct ggaacctcct gatcagtttg aaggacattg ataaactgtg attttacaat 2221 aacattatca tctgcagtta ctgtttacaa gactgctttt accttaaact ttgtagatgt 2281 ttacatcttt ttgttgtgtt ttaagatgat gttggtaatt tgtgccttta gctctgtttt 2341 attagacaga gttaaagcat gttgtcttct ttgggattac actcaggggt ctgaaaggca 2401 gtttgatttt tatttttaac acacttgaaa aaaggttgga gtagccagac tttcatatat 2461 aacttggtga ttatcaacct gttgtgtctt tatttaattt tacatctttt tgaagcactg 2521 ccacaggtta ttagccaagg tggccttcct tcacagtcat gctgcttttt tgaaaggtga 2581 atttcaacac atttagtgcc tctttcattt ctcagtatat atttcaagag cttgtgatga 2641 aatctatagg atggtaatga tggacttgtc acctgtatgg ggaatacttt tactactcag 2701 aaatgaattt atgtgctgcc atttgctata aagttgaact ttgtatggct tgaaaaagaa 2761 atgacaatat ggaacatccc aaggctgtcc catagggttg gaagttgtgt agcattcact 2821 cccttaccta ctggcattcc cagtgccctc tgtccatacc tacttctagg attgcaaagg 2881 agtcttccaa ctagagaaaa attgtccact gacatttggg atttactttt ctccaatacc 2941 tgccaataca gaaaactatt atcagttgtt attgttatcc cttgaaagcg agggtgacaa 3001 aaacaacaaa acaccgttat aaacacatca aaggttcatt ctgactgagg taagactttc 3061 caagcccttg ttagattagg ccttataaaa cttgtgtgca ttataaccta agctgtgcaa 3121 cctgtgaagc caagagtgaa ctgatgtttc atttatattt tcatccaaat gacattatct 3181 gcacgttttt aaaatttaaa aacaaaggac tatttaaaaa tacagtttat taacaaacgt 3241 gaactacttt ctgttacatt aggtgttccc tagtgtttct taatttcttt ttagaaagtg 3301 tatttttatt agtatttttc cggtgaacag aagatttgtt tggatttaaa catttactaa 3361 gacagtacct attaggaaaa ccaaatattg caaatggtca attcgatttt aatttctcaa 3421 aagatactct gttatccaga agattaaaat gcctacattg agtgcttaaa aaaaaaaaaa 3481 caactgtgat gatgtgagca gaatggcaag taagttaagc atttttgatc ctgtaatcat 3541 ggtatcatta caatgaaagg aattcacaaa ctactgccag aggaagtttg ttttttaatt 3601 taagagggaa atataaccta taaatttgtt tcttccaagc ttagctctta aatttggaga 3661 ctcaaagtta aacatcctca acagagtttt atttataatt ttgaattgtc aatttgtatt 3721 ttgctactga tctgtgatca accattttaa ctttcatctc tagggatgtt taacatttat 3781 aattgcaaaa taaaccaact ataaaaaaag aaactaagag agaattggta ctttaattac 3841 ttgtgtgttt gcaaataggc tccattttcc atgttgagta gattataacc ttattaacta 3901 tgcataggcc taagaaaggt ggcaatgaac tgtgcatgta aattttaaat gggtactttg 3961 tgcaattcgt taaaagaaga tactctatga atatgattct atatattgaa atcagaaaac 4021 ctaccaaaca aaaacatcag aagctgctgc cataatgact attttctact gtaggctgct 4081 ttggaaataa ttcccatatc cttgctttgt aagttggtaa tatcactatg catttctaca 4141 cattttataa atttgattta tgcagatttt gatacactgt atgtttctgt agaaattgta 4201 taaatattca aaattttatt aggataaatt tgagaaactt acgtatatct taattctggg 4261 ttgcttgttt tttaggtgac aaaaataaaa tattgtattt taattcaaaa aaaaaaaaaa 4321 aaaaaaaaaa aaaaaaaaa

One example of a nucleic acid sequence for human GATM is available as NCBI accession number NM_(—)001482 (gi: 126090880). This sequence is recited below for easy reference as SEQ ID NO:141.

1 ttgcgacgct cgggtctggg tccgggtccg gacgtgcaac agaagccgtc agtggccccg 61 ctggctaaaa aagggcaagc atcggaggct cgagccagcg gccgcggcgc ttcccgacag 121 ttcctaattc ggggcgctac gccggcccca ccacctgttc ccggcagcca atggggccgc 181 ggggggcggc cggggcggag cgcggctaca aaaggcctcg ggccccgcgc gcccgcccac 241 cccgctccgg gcgcgctctc gggaaggctt ggaccgacgc ggcccagagg ccaggaacat 301 tccgcgcgtg gaccagccgg gccagggcga tgctgcgggt gcggtgtctg cgcggcggga 361 gccgcggcgc cgaggcggtg cactacatcg gatctcggct tggacgaacc ttgacaggat 421 gggtgcagcg aactttccag agcacccagg cagctacggc ttcctcccgg aactcctgtg 481 cagctgacga caaagccact gagcctctgc ccaaggactg ccctgtctct tcttacaacg 541 aatgggaccc cttagaggaa gtgatagtgg gcagagcaga aaacgcctgt gttccaccgt 601 tcaccatcga ggtgaaggcc aacacatatg aaaagtactg gccattttac cagaagcaag 661 gagggcatta ttttcccaaa gatcatttga aaaaggctgt tgctgaaatt gaagaaatgt 721 gcaatatttt aaaaacggaa ggagtgacag taaggaggcc tgaccccatt gactggtcat 781 tgaagtataa aactcctgat tttgagtcta cgggtttata cagtgcaatg cctcgagaca 841 tcctgatagt tgtgggcaat gagattatcg aggctcccat ggcatggcgt tcacgcttct 901 ttgagtaccg agcgtacagg tcaattatca aagactactt ccaccgtggc gccaagtgga 961 caacagctcc taagcccaca atggctgatg agctttataa ccaggattat cccatccact 1021 ctgtagaaga cagacacaaa ttggctgctc agggaaaatt tgtgacaact gagtttgagc 1081 catgctttga tgctgctgac ttcattcgag ctggaagaga tatttttgca cagagaagcc 1141 aggttacaaa ctacctaggc attgaatgga tgcgtaggca tcttgctcca gactacagag 1201 tgcatatcat ctcctttaaa gatcccaatc ccatgcatat tgatgctacc ttcaacatca 1261 ttggacctgg tattgtgctt tccaaccctg accgaccatg tcaccagatt gatcttttca 1321 agaaagcagg atggactatc attactcctc caacaccaat catcccagac gatcatccac 1381 tctggatgtc atccaaatgg ctttccatga atgtcttaat gctagatgaa aaacgtgtta 1441 tggtggatgc caatgaagtt ccaattcaaa agatgtttga aaagctgggt atcactacca 1501 ttaaagttaa cattcgtaat gccaattccc tgggaggagg cttccattgc tggacctgcg 1561 atgtccggcg ccgaggcacc ttacagtcct acttggactg aacaggcctg atggagcttg 1621 tggctggcct cagatacacc taagaagctt aggggcaagg ttcattctcc tgctttaaaa 1681 agtgcatgaa ctgtagtgct ttaaacaatc atctccttaa caggggtcgt aagcctggtt 1741 tgcttctatt acttttcttt gacataaaga aaataacttc tgctaggtat tactctctac 1801 tcctaaagtt atttactatt tggcttcaag tataaaattt tggtgaatgt gtaccaagaa 1861 aaaattagtc acctgagtaa cttggccact aataattaac catctacctc tgtttttaat 1921 tttctttcca aaaggcagct tgaaatgttg gtcctaatct taattttttt tcctcttcta 1981 tagacttgag aatgtttttc tctaaatgag agaaagactt agaatgtaca cagatccaaa 2041 atagaatcag attatctctt tttttctaaa ggagagaaag acttagaaca tacacagatc 2101 ctaagtagaa ccaggtaatt gtctcttttt ctaataagga atttgggtaa tttttaattt 2161 tttgtttttt aaaaaataac ctagactatg caaaacatca aagtgaattt tccatgaatg 2221 tttttaatat tctcatctca acattgtgat atatgctact aaaaaccttt tcatatacat 2281 cttacctcat ttcaagtgaa ttattttaat ctttttctct ctttccaaaa atttaggaat 2341 gtttagtgta attggatttc gctatcagtt cccatcctta agttttgata ttcaatatct 2401 gatagataca ctgcatcttt ggtcatctaa gatttgttta caaatgtgca aattatttag 2461 agcatagact ttataagcat taaaaaaaac taatggaggt aaaacctaaa tgcgatgtga 2521 aataatttta gtgttgatac cgtatgtgta tttttattct aataaacttt tgtgttccag 2581 attgaaaaaa aaaaaaaaaa aa

One example of a nucleic acid sequence for human HGD is available as NCBI accession number NM_(—)000187 (gi: 115527116). This sequence is recited below for easy reference as SEQ ID NO:142.

1 ccacagttcc tttccccgat agcttcaaat tctctgcctt ttgaaataag cctactttta 61 actggaataa ataattggtc aatctctacc tcaggtgaag aggaaccaag cctctggaaa 121 cacttaggaa caaactgtaa aaaccaaagg caattgtgta accggttaaa taagcttgct 181 ggactttgtc cctgtgtatg agttagacaa ttctttcagc tagtttgagt gacgcactga 241 ccagtgaagc gcagtgaagc agtgggaacc ggaatatcca aagagtggtt tgaaggagaa 301 agaagcattg tggctttata tcctctgggc ctgggtttcc tgaagtcacc acacatagag 361 gagagagaaa atggctgagt taaagtacat ttctggattt gggaatgagt gttcttcaga 421 ggatcctcgc tgcccaggtt ccctgccaga aggacagaat aatcctcagg tctgccccta 481 caatctctat gctgagcagc tctcaggatc ggctttcact tgtccacgga gcaccaataa 541 gagaagctgg ctgtatagga ttctaccttc agtttctcac aagccctttg aatccattga 601 cgaaggccaa gtcactcaca actgggatga agttgatcct gatcctaacc agcttagatg 661 gaaaccattt gagattccaa aagcatctca gaagaaagta gactttgtga gtggcctgca 721 taccttgtgt ggagctggag acataaagtc taacaatggg cttgctatcc acattttcct 781 ctgcaatacc tccatggaga acagatgctt ttacaattca gatggggact tcttgattgt 841 tccgcagaaa gggaaccttc tcatttacac cgagtttggc aagatgcttg tacagcccaa 901 tgagatctgc gtcattcaga gaggaatgcg gttcagcata gatgtctttg aggagaccag 961 gggctacatc ttggaggtct atggtgtcca ctttgagtta cctgaccttg gaccaattgg 1021 ggccaatggc ttggccaatc ctcgtgattt cttgataccc attgcctggt atgaggatcg 1081 ccaagtacca ggtggttaca cggtcattaa taaataccag ggcaagctgt ttgctgccaa 1141 acaggatgtc tccccgttca atgttgtggc ctggcacggg aattatacac cctacaagta 1201 caacctgaag aatttcatgg ttatcaactc agtggccttt gaccatgcag acccatccat 1261 tttcacagta ttgactgcta agtctgtccg ccctggagtg gccattgctg attttgtcat 1321 cttcccacct cgatgggggg ttgctgataa gaccttcagg cctccttatt accataggaa 1381 ctgcatgagt gagttcatgg gactcatccg aggtcactat gaggcaaagc aaggtgggtt 1441 cctgccaggg ggagggagtc tacacagcac aatgaccccc catggacctg atgctgactg 1501 ctttgagaag gccagcaagg tcaagctggc acctgagagg attgccgatg gcaccatggc 1561 atttatgttt gaatcatctt taagtctggc ggtcacaaag tggggactca aggcctccag 1621 gtgtttggat gagaactacc acaagtgctg ggagccactc aagagccact tcactcccaa 1681 ctccaggaac ccagcagaac ctaattgaga ctggaacatt gctaccataa ttaagagtag 1741 atttgtgaag atttcttcag aatctcatgc tttctggtag tattggagga gggggttggt 1801 taaaatgaaa attcactttt catagtcaag taactcagaa cttttatgga aacgcatttg 1861 caaagttcta tggctgtcac cttaattact caataaactt gctggtgttc tgtggacgta

One example of a nucleic acid sequence for human HMGA2 is available as NCBI accession number NM_(—)003483 (gi: 62912480). This sequence is recited below for easy reference as SEQ ID NO:143.

1 cttgaatctt ggggcaggaa ctcagaaaac ttccagcccg ggcagcgcgc gcttggtgca 61 agactcagga gctagcagcc cgtccccctc cgactctccg gtgccgccgc tgcctgctcc 121 cgccacccta ggaggcgcgg tgccacccac tactctgtcc tctgcctgtg ctccgtgccc 181 gaccctatcc cggcggagtc tccccatcct cctttgcttt ccgactgccc aaggcacttt 241 caatctcaat ctcttctctc tctctctctc tctctctctc tctctctctc tctctctctc 301 tctctctctc gcagggtggg gggaagagga ggaggaattc tttccccgcc taacatttca 361 agggacacaa ttcactccaa gtctcttccc tttccaagcc gcttccgaag tgctcccggt 421 gcccgcaact cctgatccca acccgcgaga ggagcctctg cgacctcaaa gcctctcttc 481 cttctccctc gcttccctcc tcctcttgct acctccacct ccaccgccac ctccacctcc 541 ggcacccacc caccgccgcc gccgccaccg gcagcgcctc ctcctctcct cctcctcctc 601 ccctcttctc tttttggcag ccgctggacg tccggtgttg atggtggcag cggcggcagc 661 ctaagcaaca gcagccctcg cagcccgcca gctcgcgctc gccccgccgg cgtccccagc 721 cctatcacct catctcccga aaggtgctgg gcagctccgg ggcggtcgag gcgaagcggc 781 tgcagcggcg gtagcggcgg cgggaggcag gatgagcgca cgcggtgagg gcgcggggca 841 gccgtccact tcagcccagg gacaacctgc cgccccagcg cctcagaaga gaggacgcgg 901 ccgccccagg aagcagcagc aagaaccaac cggtgagccc tctcctaaga gacccagggg 961 aagacccaaa ggcagcaaaa acaagagtcc ctctaaagca gctcaaaaga aagcagaagc 1021 cactggagaa aaacggccaa gaggcagacc taggaaatgg ccacaacaag ttgttcagaa 1081 gaagcctgct caggaggaaa ctgaagagac atcctcacaa gagtctgccg aagaggacta 1141 gggggcgcca acgttcgatt tctacctcag cagcagttgg atcttttgaa gggagaagac 1201 actgcagtga ccacttattc tgtattgcca tggtctttcc actttcatct ggggtggggt 1261 ggggtggggt gggggagggg ggggtggggt ggggagaaat cacataacct taaaaaggac 1321 tatattaatc accttctttg taatcccttc acagtcccag gtttagtgaa aaactgctgt 1381 aaacacaggg gacacagctt aacaatgcaa cttttaatta ctgttttctt ttttcttaac 1441 ctactaatag tttgttgatc tgataagcaa gagtgggcgg gtgagaaaaa ccgaattggg 1501 tttagtcaat cactgcactg catgcaaaca agaaacgtgt cacacttgtg acgtcgggca 1561 ttcatatagg aagaacgcgg tgtgtaacac tgtgtacacc tcaaatacca ccccaaccca 1621 ctccctgtag tgaatcctct gtttagaaca ccaaagataa ggactagata ctactttctc 1681 tttttcgtat aatcttgtag acacttactt gatgattttt aactttttat ttctaaatga 1741 gacgaaatgc tgatgtatcc tttcattcag ctaacaaact agaaaaggtt atgttcattt 1801 ttcaaaaagg gaagtaagca aacaaatatt gccaactctt ctatttatgg atatcacaca 1861 tatcagcagg agtaataaat ttactcacag cacttgtttt caggacaaca cttcattttc 1921 aggaaatcta cttcctacag agccaaaatg ccatttagca ataaataaca cttgtcagcc 1981 tcagagcatt taaggaaact agacaagtaa aattatcctc tttgtaattt aatgaaaagg 2041 tacaacagaa taatgcatga tgaactcacc taattatgag gtgggaggag cgaaatctaa 2101 atttcttttg ctatagttat acatcaattt aaaaagcaaa aaaaaaaaag gggggggcaa 2161 tctctctctg tgtctttctc tctctctctt cctctccctc tctcttttca ttgtgtatca 2221 gtttccatga aagacctgaa taccacttac ctcaaattaa gcatatgtgt tacttcaagt 2281 aatacgtttt gacataagat ggttgaccaa ggtgcttttc ttcggcttga gttcaccatc 2341 tcttcattca aactgcactt ttagccagag atgcaatata tccccactac tcaatactac 2401 ctctgaatgt tacaacgaat ttacagtcta gtacttatta catgctgcta tacacaagca 2461 atgcaagaaa aaaacttact gggtaggtga ttctaatcat ctgcagttct ttttgtacac 2521 ttaattacag ttaaagaagc aatctcctta ctgtgtttca gcatgactat gtatttttct 2581 atgttttttt aattaaaaat ttttaaaata cttgtttcag cttctctgct agatttctac 2641 attaacttga aaatttttta accaagtcgc tcctaggttc ttaaggataa ttttcctcaa 2701 tcacactaca catcacacaa gatttgactg taatatttaa atattaccct ccaagtctgt 2761 acctcaaatg aattctttaa ggagatggac taattgactt gcaaagacct acctccagac 2821 ttcaaaagga atgaacttgt tacttgcagc attcatttgt tttttcaatg tttgaaatag 2881 ttcaaactgc agctaaccct agtcaaaact atttttgtaa aagacatttg atagaaagga 2941 acacgttttt acatactttt gcaaaataag taaataataa ataaaataaa agccaacctt 3001 caaagaaact tgaagctttg taggtgagat gcaacaagcc ctgcttttgc ataatgcaat 3061 caaaaatatg tgtttttaag attagttgaa tataagaaaa tgcttgacaa atattttcat 3121 gtattttaca caaatgtgat ttttgtaata tgtctcaacc agatttattt taaacgcttc 3181 ttatgtagag tttttatgcc tttctctcct agtgagtgtg ctgacttttt aacatggtat 3241 tatcaactgg gccaggaggt agtttctcat gacggctttt gtcagtatgg cttttagtac 3301 tgaagccaaa tgaaactcaa aaccatctct cttccagctg cttcagggag gtagtttcaa 3361 aggccacata cctctctgag actggcagat cgctcactgt tgtgaatcac caaaggagct 3421 atggagagaa ttaaaactca acattactgt taactgtgcg ttaaataagc aaataaacag 3481 tggctcataa aaataaaagt cgcattccat atctttggat gggcctttta gaaacctcat 3541 tggccagctc ataaaatgga agcaattgct catgttggcc aaacatggtg caccgagtga 3601 tttccatctc tggtaaagtt acacttttat ttcctgtatg ttgtacaatc aaaacacact 3661 actacctctt aagtcccagt atacctcatt tttcatactg aaaaaaaaag cttgtggcca 3721 atggaacagt aagaacatca taaaattttt atatatatag tttatttttg tgggagataa 3781 attttatagg actgttcttt gctgttgttg gtcgcagcta cataagactg gacatttaac 3841 ttttctacca tttctgcaag ttaggtatgt ttgcaggaga aaagtatcaa gacgtttaac 3901 tgcagttgac tttctccctg ttcctttgag tgtcttctaa ctttattctt tgttctttat 3961 gtagaattgc tgtctatgat tgtactttga atcgcttgct tgttgaaaat atttctctag 4021 tgtattatca ctgtctgttc tgcacaataa acataacagc ctctgtgatc cccatgtgtt 4081 ttgattcctg ctctttgtta cagttccatt aaatgagtaa taaagtttgg tcaaaacaga 4141 aaaaaaaaaa

One example of a nucleic acid sequence for human IGFBP6 is available as NCBI accession number NM_(—)002178 (gi: 49574524). This sequence is recited below for easy reference as SEQ ID NO:144.

1 gcggcggcgg gcagcagctg cgctgcgact gctctggaag gagaggacgg ggcacaaacc 61 ctgaccatga ccccccacag gctgctgcca ccgctgctgc tgctgctagc tctgctgctc 121 gctgccagcc caggaggcgc cttggcgcgg tgcccaggct gcgggcaagg ggtgcaggcg 181 ggttgtccag ggggctgcgt ggaggaggag gatggggggt cgccagccga gggctgcgcg 241 gaagctgagg gctgtctcag gagggagggg caggagtgcg gggtctacac ccctaactgc 301 gccccaggac tgcagtgcca tccgcccaag gacgacgagg cgcctttgcg ggcgctgctg 361 ctcggccgag gccgctgcct tccggcccgc gcgcctgctg ttgcagagga gaatcctaag 421 gagagtaaac cccaagcagg cactgcccgc ccacaggatg tgaaccgcag agaccaacag 481 aggaatccag gcacctctac cacgccctcc cagcccaatt ctgcgggtgt ccaagacact 541 gagatgggcc catgccgtag acatctggac tcagtgctgc agcaactcca gactgaggtc 601 taccgagggg ctcaaacact ctacgtgccc aattgtgacc atcgaggctt ctaccggaag 661 cggcagtgcc gctcctccca ggggcagcgc cgaggtccct gctggtgtgt ggatcggatg 721 ggcaagtccc tgccagggtc tccagatggc aatggaagct cctcctgccc cactgggagt 781 agcggctaaa gctgggggat agaggggctg cagggccact ggaaggaaca tggagctgtc 841 atcactcaac aaaaaaccga ggccctcaat ccaccttcag gccccgcccc atgggcccct 901 caccgctggt tggaaagagt gttggtgttg gctggggtgt caataaagct gtgcttgggg 961 tcgctgaaaa aaaaaaaaaa

One example of a nucleic acid sequence for human KIT is available as NCBI accession number NM_(—)000222 (gi: 148005048). This sequence is recited below for easy reference as SEQ ID NO:145.

1 tctgggggct cggctttgcc gcgctcgctg cacttgggcg agagctggaa cgtggaccag 61 agctcggatc ccatcgcagc taccgcgatg agaggcgctc gcggcgcctg ggattttctc 121 tgcgttctgc tcctactgct tcgcgtccag acaggctctt ctcaaccatc tgtgagtcca 181 ggggaaccgt ctccaccatc catccatcca ggaaaatcag acttaatagt ccgcgtgggc 241 gacgagatta ggctgttatg cactgatccg ggctttgtca aatggacttt tgagatcctg 301 gatgaaacga atgagaataa gcagaatgaa tggatcacgg aaaaggcaga agccaccaac 361 accggcaaat acacgtgcac caacaaacac ggcttaagca attccattta tgtgtttgtt 421 agagatcctg ccaagctttt ccttgttgac cgctccttgt atgggaaaga agacaacgac 481 acgctggtcc gctgtcctct cacagaccca gaagtgacca attattccct caaggggtgc 541 caggggaagc ctcttcccaa ggacttgagg tttattcctg accccaaggc gggcatcatg 601 atcaaaagtg tgaaacgcgc ctaccatcgg ctctgtctgc attgttctgt ggaccaggag 661 ggcaagtcag tgctgtcgga aaaattcatc ctgaaagtga ggccagcctt caaagctgtg 721 cctgttgtgt ctgtgtccaa agcaagctat cttcttaggg aaggggaaga attcacagtg 781 acgtgcacaa taaaagatgt gtctagttct gtgtactcaa cgtggaaaag agaaaacagt 841 cagactaaac tacaggagaa atataatagc tggcatcacg gtgacttcaa ttatgaacgt 901 caggcaacgt tgactatcag ttcagcgaga gttaatgatt ctggagtgtt catgtgttat 961 gccaataata cttttggatc agcaaatgtc acaacaacct tggaagtagt agataaagga 1021 ttcattaata tcttccccat gataaacact acagtatttg taaacgatgg agaaaatgta 1081 gatttgattg ttgaatatga agcattcccc aaacctgaac accagcagtg gatctatatg 1141 aacagaacct tcactgataa atgggaagat tatcccaagt ctgagaatga aagtaatatc 1201 agatacgtaa gtgaacttca tctaacgaga ttaaaaggca ccgaaggagg cacttacaca 1261 ttcctagtgt ccaattctga cgtcaatgct gccatagcat ttaatgttta tgtgaataca 1321 aaaccagaaa tcctgactta cgacaggctc gtgaatggca tgctccaatg tgtggcagca 1381 ggattcccag agcccacaat agattggtat ttttgtccag gaactgagca gagatgctct 1441 gcttctgtac tgccagtgga tgtgcagaca ctaaactcat ctgggccacc gtttggaaag 1501 ctagtggttc agagttctat agattctagt gcattcaagc acaatggcac ggttgaatgt 1561 aaggcttaca acgatgtggg caagacttct gcctatttta actttgcatt taaaggtaac 1621 aacaaagagc aaatccatcc ccacaccctg ttcactcctt tgctgattgg tttcgtaatc 1681 gtagctggca tgatgtgcat tattgtgatg attctgacct acaaatattt acagaaaccc 1741 atgtatgaag tacagtggaa ggttgttgag gagataaatg gaaacaatta tgtttacata 1801 gacccaacac aacttcctta tgatcacaaa tgggagtttc ccagaaacag gctgagtttt 1861 gggaaaaccc tgggtgctgg agctttcggg aaggttgttg aggcaactgc ttatggctta 1921 attaagtcag atgcggccat gactgtcgct gtaaagatgc tcaagccgag tgcccatttg 1981 acagaacggg aagccctcat gtctgaactc aaagtcctga gttaccttgg taatcacatg 2041 aatattgtga atctacttgg agcctgcacc attggagggc ccaccctggt cattacagaa 2101 tattgttgct atggtgatct tttgaatttt ttgagaagaa aacgtgattc atttatttgt 2161 tcaaagcagg aagatcatgc agaagctgca ctttataaga atcttctgca ttcaaaggag 2221 tcttcctgca gcgatagtac taatgagtac atggacatga aacctggagt ttcttatgtt 2281 gtcccaacca aggccgacaa aaggagatct gtgagaatag gctcatacat agaaagagat 2341 gtgactcccg ccatcatgga ggatgacgag ttggccctag acttagaaga cttgctgagc 2401 ttttcttacc aggtggcaaa gggcatggct ttcctcgcct ccaagaattg tattcacaga 2461 gacttggcag ccagaaatat cctccttact catggtcgga tcacaaagat ttgtgatttt 2521 ggtctagcca gagacatcaa gaatgattct aattatgtgg ttaaaggaaa cgctcgacta 2581 cctgtgaagt ggatggcacc tgaaagcatt ttcaactgtg tatacacgtt tgaaagtgac 2641 gtctggtcct atgggatttt tctttgggag ctgttctctt taggaagcag cccctatcct 2701 ggaatgccgg tcgattctaa gttctacaag atgatcaagg aaggcttccg gatgctcagc 2761 cctgaacacg cacctgctga aatgtatgac ataatgaaga cttgctggga tgcagatccc 2821 ctaaaaagac caacattcaa gcaaattgtt cagctaattg agaagcagat ttcagagagc 2881 accaatcata tttactccaa cttagcaaac tgcagcccca accgacagaa gcccgtggta 2941 gaccattctg tgcggatcaa ttctgtcggc agcaccgctt cctcctccca gcctctgctt 3001 gtgcacgacg atgtctgagc agaatcagtg tttgggtcac ccctccagga atgatctctt 3061 cttttggctt ccatgatggt tattttcttt tctttcaact tgcatccaac tccaggatag 3121 tgggcacccc actgcaatcc tgtctttctg agcacacttt agtggccgat gatttttgtc 3181 atcagccacc atcctattgc aaaggttcca actgtatata ttcccaatag caacgtagct 3241 tctaccatga acagaaaaca ttctgatttg gaaaaagaga gggaggtatg gactgggggc 3301 cagagtcctt tccaaggctt ctccaattct gcccaaaaat atggttgata gtttacctga 3361 ataaatggta gtaatcacag ttggccttca gaaccatcca tagtagtatg atgatacaag 3421 attagaagct gaaaacctaa gtcctttatg tggaaaacag aacatcatta gaacaaagga 3481 cagagtatga acacctgggc ttaagaaatc tagtatttca tgctgggaat gagacatagg 3541 ccatgaaaaa aatgatcccc aagtgtgaac aaaagatgct cttctgtgga ccactgcatg 3601 agcttttata ctaccgacct ggtttttaaa tagagtttgc tattagagca ttgaattgga 3661 gagaaggcct ccctagccag cacttgtata tacgcatcta taaattgtcc gtgttcatac 3721 atttgagggg aaaacaccat aaggtttcgt ttctgtatac aaccctggca ttatgtccac 3781 tgtgtataga agtagattaa gagccatata agtttgaagg aaacagttaa taccattttt 3841 taaggaaaca atataaccac aaagcacagt ttgaacaaaa tctcctcttt tagctgatga 3901 acttattctg tagattctgt ggaacaagcc tatcagcttc agaatggcat tgtactcaat 3961 ggatttgatg ctgtttgaca aagttactga ttcactgcat ggctcccaca ggagtgggaa 4021 aacactgcca tcttagtttg gattcttatg tagcaggaaa taaagtatag gtttagcctc 4081 cttcgcaggc atgtcctgga caccgggcca gtatctatat atgtgtatgt acgtttgtat 4141 gtgtgtagac aaatatttgg aggggtattt ttgccctgag tccaagaggg tcctttagta 4201 cctgaaaagt aacttggctt tcattattag tactgctctt gtttcttttc acatagctgt 4261 ctagagtagc ttaccagaag cttccatagt ggtgcagagg aagtggaagg catcagtccc 4321 tatgtatttg cagttcacct gcacttaagg cactctgtta tttagactca tcttactgta 4381 cctgttcctt agaccttcca taatgctact gtctcactga aacatttaaa ttttaccctt 4441 tagactgtag cctggatatt attcttgtag tttacctctt taaaaacaaa acaaaacaaa 4501 acaaaaaact ccccttcctc actgcccaat ataaaaggca aatgtgtaca tggcagagtt 4561 tgtgtgttgt cttgaaagat tcaggtatgt tgcctttatg gtttccccct tctacatttc 4621 ttagactaca tttagagaac tgtggccgtt atctggaagt aaccatttgc actggagttc 4681 tatgctctcg cacctttcca aagttaacag attttggggt tgtgttgtca cccaagagat 4741 tgttgtttgc catactttgt ctgaaaaatt cctttgtgtt tctattgact tcaatgatag 4801 taagaaaagt ggttgttagt tatagatgtc taggtacttc aggggcactt cattgagagt 4861 tttgtcttgg atattcttga aagtttatat ttttataatt ttttcttaca tcagatgttt 4921 ctttgcagtg gcttaatgtt tgaaattatt ttgtggcttt ttttgtaaat attgaaatgt 4981 agcaataatg tcttttgaat attcccaagc ccatgagtcc ttgaaaatat tttttatata 5041 tacagtaact ttatgtgtaa atacataagc ggcgtaagtt taaaggatgt tggtgttcca 5101 cgtgttttat tcctgtatgt tgtccaattg ttgacagttc tgaagaattc taataaaatg 5161 tacatatata aatcaaaaaa aaaaaaaaaa

One example of a nucleic acid sequence for human LRP4 is available as NCBI accession number NM_(—)002334 (gi: 157384997). This sequence is recited below for easy reference as SEQ ID NO:146.

1 gcggcggcgg cccgagggcg acttgcgggg cgcgcaggcc gccgtgcacc cgggacgctt 61 ccccctcggg gaccctccgc gggcttctcc gccgcgccgt ccggcgggag ccggcgggac 121 cccgggcgag cggcgcgggc ggcaccatga ggcggcagtg gggcgcgctg ctgcttggcg 181 ccctgctctg cgcacacggc ctggccagca gccccgagtg tgcttgtggt cggagccact 241 tcacatgtgc agtgagtgct cttggagagt gtacctgcat ccctgcccag tggcagtgtg 301 atggagacaa tgactgcggg gaccacagcg atgaggatgg atgtatacta cctacctgtt 361 cccctcttga ctttcactgt gacaatggca agtgcatccg ccgctcctgg gtgtgtgacg 421 gggacaacga ctgtgaggat gactcggatg agcaggactg tcccccccgg gagtgtgagg 481 aggacgagtt tccctgccag aatggctact gcatccggag tctgtggcac tgcgatggtg 541 acaatgactg tggcgacaac agcgatgagc agtgtgacat gcgcaagtgc tccgacaagg 601 agttccgctg tagtgacgga agctgcattg ctgagcattg gtactgcgac ggtgacaccg 661 actgcaaaga tggctccgat gaggagaact gtccctcagc agtgccagcg cccccctgca 721 acctggagga gttccagtgt gcctatggac gctgcatcct cgacatctac cactgcgatg 781 gcgacgatga ctgtggagac tggtcagacg agtctgactg ctcctcccac cagccctgcc 841 gctctgggga gttcatgtgt gacagtggcc tgtgcatcaa tgcaggctgg cgctgcgatg 901 gtgacgcgga ctgtgatgac cagtctgatg agcgcaactg caccacctcc atgtgtacgg 961 cagaacagtt ccgctgtcac tcaggccgct gtgtccgcct gtcctggcgc tgtgatgggg 1021 aggacgactg tgcagacaac agcgatgaag agaactgtga gaatacagga agcccccaat 1081 gtgccttgga ccagttcctg tgttggaatg ggcgctgcat tgggcagagg aagctgtgca 1141 acggggtcaa cgactgtggt gacaacagcg acgaaagccc acagcagaat tgccggcccc 1201 ggacgggtga ggagaactgc aatgttaaca acggtggctg tgcccagaag tgccagatgg 1261 tgcggggggc agtgcagtgt acctgccaca caggctaccg gctcacagag gatgggcaca 1321 cgtgccaaga tgtgaatgaa tgtgccgagg aggggtattg cagccagggc tgcaccaaca 1381 gcgaaggggc tttccaatgc tggtgtgaaa caggctatga actacggccc gaccggcgca 1441 gctgcaaggc tctggggcca gagcctgtgc tgctgttcgc caatcgcatc gacatccggc 1501 aggtgctgcc acaccgctct gagtacacac tgctgcttaa caacctggag aatgccattg 1561 cccttgattt ccaccaccgc cgcgagcttg tcttctggtc agatgtcacc ctggaccgga 1621 tcctccgtgc caacctcaac ggcagcaacg tggaggaggt tgtgtctact gggctggaga 1681 gcccaggggg cctggctgtg gattgggtcc atgacaaact ctactggacc gactcaggca 1741 cctcgaggat tgaggtggcc aatctggatg gggcccaccg gaaagtgttg ctgtggcaga 1801 acctggagaa gccccgggcc attgccttgc atcccatgga gggtaccatt tactggacag 1861 actggggcaa caccccccgt attgaggcct ccagcatgga tggctctgga cgccgcatca 1921 ttgccgatac ccatctcttc tggcccaatg gcctcaccat cgactatgcc gggcgccgta 1981 tgtactgggt ggatgctaag caccatgtca tcgagagggc caatctggat gggagtcacc 2041 gtaaggctgt cattagccag ggcctcccgc atcccttcgc catcacagtg tttgaagaca 2101 gcctgtactg gacagactgg cacaccaaga gcatcaatag cgctaacaaa tttacgggga 2161 agaaccagga aatcattcgc aacaaactcc acttccctat ggacatccac accttgcacc 2221 cccagcgcca acctgcaggg aaaaaccgct gtggggacaa caacggaggc tgcacgcacc 2281 tgtgtctgcc cagtggccag aactacacct gtgcctgccc cactggcttc cgcaagatca 2341 gcagccacgc ctgtgcccag agtcttgaca agttcctgct ttttgcccga aggatggaca 2401 tccgtcgaat cagctttgac acagaggacc tgtctgatga tgtcatccca ctggctgacg 2461 tgcgcagtgc tgtggccctt gactgggact cccgggatga ccacgtgtac tggacagatg 2521 tcagcactga taccatcagc agggccaagt gggatggaac aggacaggag gtggtagtgg 2581 ataccagttt ggagagccca gctggcctgg ccattgattg ggtcaccaac aaactgtact 2641 ggacagatgc aggtacagac cggattgaag tagccaacac agatggcagc atgagaacag 2701 tactcatctg ggagaacctt gatcgtcctc gggacatcgt ggtggaaccc atgggcgggt 2761 acatgtattg gactgactgg ggtgcgagcc ccaagattga acgagctggc atggatgcct 2821 caggccgcca agtcattatc tcttctaatc tgacctggcc taatgggtta gctattgatt 2881 atgggtccca gcgtctatac tgggctgacg ccggcatgaa gacaattgaa tttgctggac 2941 tggatggcag taagaggaag gtgctgattg gaagccagct cccccaccca tttgggctga 3001 ccctctatgg agagcgcatc tattggactg actggcagac caagagcata cagagcgctg 3061 accggctgac agggctggac cgggagactc tgcaggagaa cctggaaaac ctaatggaca 3121 tccatgtctt ccaccgccgc cggcccccag tgtctacacc atgtgctatg gagaatggcg 3181 gctgtagcca cctgtgtctt aggtccccaa atccaagcgg attcagctgt acctgcccca 3241 caggcatcaa cctgctgtct gatggcaaga cctgctcacc aggcatgaac agtttcctca 3301 tcttcgccag gaggatagac attcgcatgg tctccctgga catcccttat tttgctgatg 3361 tggtggtacc aatcaacatt accatgaaga acaccattgc cattggagta gacccccagg 3421 aaggaaaggt gtactggtct gacagcacac tgcacaggat cagtcgtgcc aatctggatg 3481 gctcacagca tgaggacatc atcaccacag ggctacagac cacagatggg ctcgcggttg 3541 atgccattgg ccggaaagta tactggacag acacgggaac aaaccggatt gaagtgggca 3601 acctggacgg gtccatgcgg aaagtgttgg tgtggcagaa ccttgacagt ccccgggcca 3661 tcgtactgta ccatgagatg gggtttatgt actggacaga ctggggggag aatgccaagt 3721 tagagcggtc cggaatggat ggctcagacc gcgcggtgct catcaacaac aacctaggat 3781 ggcccaatgg actgactgtg gacaaggcca gctcccaact gctatgggcc gatgcccaca 3841 ccgagcgaat tgaggctgct gacctgaatg gtgccaatcg gcatacattg gtgtcaccgg 3901 tgcagcaccc atatggcctc accctgctcg actcctatat ctactggact gactggcaga 3961 ctcggagcat ccaccgtgct gacaagggta ctggcagcaa tgtcatcctc gtgaggtcca 4021 acctgccagg cctcatggac atgcaggctg tggaccgggc acagccacta ggttttaaca 4081 agtgcggctc gagaaatggc ggctgctccc acctctgctt gcctcggcct tctggcttct 4141 cctgtgcctg ccccactggc atccagctga agggagatgg gaagacctgt gatccctctc 4201 ctgagaccta cctgctcttc tccagccgtg gctccatccg gcgtatctca ctggacacca 4261 gtgaccacac cgatgtgcat gtccctgttc ctgagctcaa caatgtcatc tccctggact 4321 atgacagcgt ggatggaaag gtctattaca cagatgtgtt cctggatgtt atcaggcgag 4381 cagacctgaa cggcagcaac atggagacag tgatcgggcg agggctgaag accactgacg 4441 ggctggcagt ggactgggtg gccaggaacc tgtactggac agacacaggt cgaaatacca 4501 ttgaggcgtc caggctggat ggttcctgcc gcaaagtact gatcaacaat agcctggatg 4561 agccccgggc cattgctgtt ttccccagga aggggtacct cttctggaca gactggggcc 4621 acattgccaa gatcgaacgg gcaaacttgg atggttctga gcggaaggtc ctcatcaaca 4681 cagacctggg ttggcccaat ggccttaccc tggactatga tacccgcagg atctactggg 4741 tggatgcgca tctggaccgg atcgagagtg ctgacctcaa tgggaaactg cggcaggtct 4801 tggtcagcca tgtgtcccac ccctttgccc tcacacagca agacaggtgg atctactgga 4861 cagactggca gaccaagtca atccagcgtg ttgacaaata ctcaggccgg aacaaggaga 4921 cagtgctggc aaatgtggaa ggactcatgg atatcatcgt ggtttcccct cagcggcaga 4981 cagggaccaa tgcctgtggt gtgaacaatg gtggctgcac ccacctctgc tttgccagag 5041 cctcggactt cgtatgtgcc tgtcctgacg aacctgatag ccggccctgc tcccttgtgc 5101 ctggcctggt accaccagct cctagggcta ctggcatgag tgaaaagagc ccagtgctac 5161 ccaacacacc acctaccacc ttgtattctt caaccacccg gacccgcacg tctctggagg 5221 aggtggaagg aagatgctct gaaagggatg ccaggctggg cctctgtgca cgttccaatg 5281 acgctgttcc tgctgctcca ggggaaggac ttcatatcag ctacgccatt ggtggactcc 5341 tcagtattct gctgattttg gtggtgattg cagctttgat gctgtacaga cacaaaaaat 5401 ccaagttcac tgatcctgga atggggaacc tcacctacag caacccctcc taccgaacat 5461 ccacacagga agtgaagatt gaagcaatcc ccaaaccagc catgtacaac cagctgtgct 5521 ataagaaaga gggagggcct gaccataact acaccaagga gaagatcaag atcgtagagg 5581 gaatctgcct cctgtctggg gatgatgctg agtgggatga cctcaagcaa ctgcgaagct 5641 cacggggggg cctcctccgg gatcatgtat gcatgaagac agacacggtg tccatccagg 5701 ccagctctgg ctccctggat gacacagaga cggagcagct gttacaggaa gagcagtctg 5761 agtgtagcag cgtccatact gcagccactc cagaaagacg aggctctctg ccagacacgg 5821 gctggaaaca tgaacgcaag ctctcctcag agagccaggt ctaaatgccc acattctctt 5881 ccctgcctgc ctgttccttc tcctttatgg acgtctagtc cttgtgctcg cttacaccgc 5941 aggccccgct tctgtgtgct tgtcctcctc ctcctcccac cccataactg ttcctaagcc 6001 ttcaccggag ctgtttacca cgtgagtcca taactacctg tgcacaagaa atgatggcac 6061 atcacgagaa tttagacctg gattttacca tgaacctcac atcttgtact ccatcctggg 6121 ccccctgaaa ctgcttattc gtgattcctc accagcgtag agctccacct cccctttccc 6181 cagtaccctc agtgcctgct tctcagtgct gatgcagctg atgacccagg actgcgctct 6241 gccccatcac agccagcatg actgcttctc tgagagaact tgcccatcag gggctgggac 6301 atgggggtgt gggtaaagac agggatgaag gatagaggct gagagaagaa ggaagaatca 6361 gcccagcagg tatgggcatc tgggaaacct ccagcctcaa gtgtgttggt aacatgaaaa 6421 agctttgggg ggtagttgga tctgggtgtc tggtccattg ctggcagtgg acattattct 6481 tgccctaaga gacactgcct tttcagcagc agatactggt gagatggggg tggctcaggc 6541 tgttcttcct cctcctagaa tgtctggagc tgtttctaca ttcagataac tgggtcccct 6601 atcacaaggc tactggctaa taggaattcc ctcctggtgc caccactggc cagtaccttt 6661 cctaagtctt tgctcaaatt aaccaggttg tgagccagtg gcttgagtga atgttaggcc 6721 ttgggggctg agtctctgaa aagtctaaga agctctgcct agaccaaata tggtatacct 6781 cctgacccct ctctccctca tgtcctggga ttctggggaa gagacctaga aacaagcttt 6841 caaagaaaaa ccagaagttg tcataaatgg tcagaaagaa cgatcaggtt ggagacttgg 6901 gaaacccagg gcctaaagag aagtatccat gagggtcaaa cttcctgttg aacttcctat 6961 gttctttctc aagtgctcag ggatctaagt tagtggacag caagcctgtg gctacggggt 7021 ggtgatgttc ctcttccagc tgtcccctca gctaaggggc ttagtttcca tgtgggatgc 7081 catcacttgg ttcatgctca ttcacacaaa gggcacgtgt ctcagcctgg tatcagggaa 7141 attgagactt atttttgccc taaaacgtct ccctagctgt tcttcgtggg gtttttttgt 7201 ttgttttttt gcctaatttg ctttttctga ccaagccttg tggcaccagc aatctccaaa 7261 gtcctgtggt gggagggctg aataaataaa aatacaaaga ggtgggtaag gagtaggaag 7321 gtagagagca ccactgatga ggccctccta gcccatggca gacccagacc tcttctcccc 7381 caggaattag aagtggcagg agagaacaac aggggctggg aatggagggg agaatttcta 7441 ggggaagttt cctgagttga aacttctcct gtggttactg gtattgagaa atcagctacc 7501 aaagtgaaaa aggacaagat caattctttt ctagtcagtt ctaagactgc tagagagaga 7561 taccaggccc ttagccttgc tctcagtagc gtcagcccca gttctgagcc tccccacatt 7621 acacttaaca agcagtaaag gagtgagcac tttgggtcct tagactcatg tctggggagg 7681 aagagcaagt agaaaagtgg cattttcttg attggaaagg gggaaggatc ttattgcact 7741 tgggctgttc agaatgtaga aaggacatat ttgaggaagt atctatttga gcactgattt 7801 actctgtaaa aagcaaaatc tctctgtcct aaactaatgg aagcgattct cccatgctca 7861 tgtgtaatgg ttttaacgtt actcactgga gagattggac tttctggagt tatttaacca 7921 ctatgttcag tattttagga ctttatgata atttaatata aatttagctt ttcttaatca 7981 aaaaaaaaaa aaaaaaaa

One example of a nucleic acid sequence for human MATN2 is available as NCBI accession number NM_(—)002380 (gi: 62548859). This sequence is recited below for easy reference as SEQ ID NO:147.

1 gcgagcgaag ggagcgctct gggatgggac ttggagcaag cggcggcggc ggagacagag 61 gcagaggcag aagctggggc tccgtcctcg cctcccacga gcgatccccg aggagagccg 121 cggccctcgg cgaggcgaag aggccgacga ggaagacccg ggtggctgcg cccctgcctc 181 gcttcccagg cgccggcggc tgcagccttg cccctcttgc tcgccttgaa aatggaaaag 241 atgctcgcag gctgctttct gctgatcctc ggacagatcg tcctcctccc tgccgaggcc 301 agggagcggt cacgtgggag gtccatctct aggggcagac acgctcggac ccacccgcag 361 acggcccttc tggagagttc ctgtgagaac aagcgggcag acctggtttt catcattgac 421 agctctcgca gtgtcaacac ccatgactat gcaaaggtca aggagttcat cgtggacatc 481 ttgcaattct tggacattgg tcctgatgtc acccgagtgg gcctgctcca atatggcagc 541 actgtcaaga atgagttctc cctcaagacc ttcaagagga agtccgaggt ggagcgtgct 601 gtcaagagga tgcggcatct gtccacgggc accatgactg ggctggccat ccagtatgcc 661 ctgaacatcg cattctcaga agcagagggg gcccggcccc tgagggagaa tgtgccacgg 721 gtcataatga tcgtgacaga tgggagacct caggactccg tggccgaggt ggctgctaag 781 gcacgggaca cgggcatcct aatctttgcc attggtgtgg gccaggtaga cttcaacacc 841 ttgaagtcca ttgggagtga gccccatgag gaccatgtct tccttgtggc caatttcagc 901 cagattgaga cgctgacctc cgtgttccag aagaagttgt gcacggccca catgtgcagc 961 accctggagc ataactgtgc ccacttctgc atcaacatcc ctggctcata cgtctgcagg 1021 tgcaaacaag gctacattct caactcggat cagacgactt gcagaatcca ggatctgtgt 1081 gccatggagg accacaactg tgagcagctc tgtgtgaatg tgccgggctc cttcgtctgc 1141 cagtgctaca gtggctacgc cctggctgag gatgggaaga ggtgtgtggc tgtggactac 1201 tgtgcctcag aaaaccacgg atgtgaacat gagtgtgtaa atgctgatgg ctcctacctt 1261 tgccagtgcc atgaaggatt tgctcttaac ccagataaaa aaacgtgcac aaagatagac 1321 tactgtgcct catctaatca cggatgtcag cacgagtgtg ttaacacaga tgattcctat 1381 tcctgccact gcctgaaagg ctttaccctg aatccagata agaaaacctg cagaaggatc 1441 aactactgtg cactgaacaa accgggctgt gagcatgagt gcgtcaacat ggaggagagc 1501 tactactgcc gctgccaccg tggctacact ctggacccca atggcaaaac ctgcagccga 1561 gtggaccact gtgcacagca ggaccatggc tgtgagcagc tgtgtctgaa cacggaggat 1621 tccttcgtct gccagtgctc agaaggcttc ctcatcaacg aggacctcaa gacctgctcc 1681 cgggtggatt actgcctgct gagtgaccat ggttgtgaat actcctgtgt caacatggac 1741 agatcctttg cctgtcagtg tcctgaggga cacgtgctcc gcagcgatgg gaagacgtgt 1801 gcaaaattgg actcttgtgc tctgggggac cacggttgtg aacattcgtg tgtaagcagt 1861 gaagattcgt ttgtgtgcca gtgctttgaa ggttatatac tccgtgaaga tggaaaaacc 1921 tgcagaagga aagatgtctg ccaagctata gaccatggct gtgaacacat ttgtgtgaac 1981 agtgatgact catacacgtg cgagtgcttg gagggattcc ggctcgctga ggatgggaaa 2041 cgctgccgaa ggaaggatgt ctgcaaatca acccaccatg gctgcgaaca catttgtgtt 2101 aataatggga attcctacat ctgcaaatgc tcagagggat ttgttctagc tgaggacgga 2161 agacggtgca agaaatgcac tgaaggccca attgacctgg tctttgtgat cgatggatcc 2221 aagagtcttg gagaagagaa ttttgaggtc gtgaagcagt ttgtcactgg aattatagat 2281 tccttgacaa tttcccccaa agccgctcga gtggggctgc tccagtattc cacacaggtc 2341 cacacagagt tcactctgag aaacttcaac tcagccaaag acatgaaaaa agccgtggcc 2401 cacatgaaat acatgggaaa gggctctatg actgggctgg ccctgaaaca catgtttgag 2461 agaagtttta cccaaggaga aggggccagg cccctttcca caagggtgcc cagagcagcc 2521 attgtgttca ccgacggacg ggctcaggat gacgtctccg agtgggccag taaagccaag 2581 gccaatggta tcactatgta tgctgttggg gtaggaaaag ccattgagga ggaactacaa 2641 gagattgcct ctgagcccac aaacaagcat ctcttctatg ccgaagactt cagcacaatg 2701 gatgagataa gtgaaaaact caagaaaggc atctgtgaag ctctagaaga ctccgatgga 2761 agacaggact ctccagcagg ggaactgcca aaaacggtcc aacagccaac agaatctgag 2821 ccagtcacca taaatatcca agacctactt tcctgttcta attttgcagt gcaacacaga 2881 tatctgtttg aagaagacaa tcttttacgg tctacacaaa agctttccca ttcaacaaaa 2941 ccttcaggaa gccctttgga agaaaaacac gatcaatgca aatgtgaaaa ccttataatg 3001 ttccagaacc ttgcaaacga agaagtaaga aaattaacac agcgcttaga agaaatgaca 3061 cagagaatgg aagccctgga aaatcgcctg agatacagat gaagattaga aatcgcgaca 3121 catttgtagt cattgtatca cggattacaa tgaacgcagt gcagagcccc aaagctcagg 3181 ctattgttaa atcaataatg ttgtgaagta aaacaatcag tactgagaaa cctggtttgC 3241 cacagaacaa agacaagaag tatacactaa cttgtataaa tttatctagg aaaaaaatcc 3301 ttcagaattc taagatgaat ttaccaggtg agaatgaata agctatgcaa ggtattttgt 3361 aatatactgt ggacacaact tgcttctgcc tcatcctgcc ttagtgtgca atctcatttg 3421 actatacgat aaagtttgca cagtcttact tctgtagaac actggccata ggaaatgctg 3481 tttttttgta ctggacttta ccttgatata tgtatatgga tgtatgcata aaatcatagg 3541 acatatgtac ttgtggaaca agttggattt tttatacaat attaaaattc accacttcag 3601 agaatggtat tcagtgcaaa aattcttagt ttaactttaa atggaagata tgtatgtatg 3661 agaaatggcc aacatgccta tgaaaaaaat gctgaatctc atcagtaatc aggaaaatgc 3721 aggttaaaac aataccattt ttcacccatc agcttagcaa aaatgagtat attttttaac 3781 aagtgttggt aaggatgtgg aaatgtgagg ttcttgtagt aagaatgcaa atggcactct 3841 ttgtagagta agtctgttga catctcataa aactgaaaat gcacacaacc ctgtaaatct 3901 agcaactgca ctcagttgat ttcagcccat acatacaaag agacctgcat aagaatgtta 3961 ctaggctttg taaaagcaaa aaataaggaa caacttaaac atcatcagaa ggggaactga 4021 taaactctgg tgtaatccat accacagaaa tacaacaccg catgtacagg aatgtgctac 4081 atctatacaa ataaatggtc aaactcaaaa aaaaaaaaaa aa

One example of a nucleic acid sequence for human MET is available as NCBI accession number NM_(—)001127500 (gi: 188595715). This sequence is recited below for easy reference as SEQ ID NO:148.

1 gccctcgccg cccgcggcgc cccgagcgct ttgtgagcag atgcggagcc gagtggaggg 61 cgcgagccag atgcggggcg acagctgact tgctgagagg aggcggggag gcgcggagcg 121 cgcgtgtggt ccttgcgccg ctgacttctc cactggttcc tgggcaccga aagataaacc 181 tctcataatg aaggcccccg ctgtgcttgc acctggcatc ctcgtgctcc tgtttacctt 241 ggtgcagagg agcaatgggg agtgtaaaga ggcactagca aagtccgaga tgaatgtgaa 301 tatgaagtat cagcttccca acttcaccgc ggaaacaccc atccagaatg tcattctaca 361 tgagcatcac attttccttg gtgccactaa ctacatttat gttttaaatg aggaagacct 421 tcagaaggtt gctgagtaca agactgggcc tgtgctggaa cacccagatt gtttcccatg 481 tcaggactgc agcagcaaag ccaatttatc aggaggtgtt tggaaagata acatcaacat 541 ggctctagtt gtcgacacct actatgatga tcaactcatt agctgtggca gcgtcaacag 601 agggacctgc cagcgacatg tctttcccca caatcatact gctgacatac agtcggaggt 661 tcactgcata ttctccccac agatagaaga gcccagccag tgtcctgact gtgtggtgag 721 cgccctggga gccaaagtcc tttcatctgt aaaggaccgg ttcatcaact tctttgtagg 781 caataccata aattcttctt atttcccaga tcatccattg cattcgatat cagtgagaag 841 gctaaaggaa acgaaagatg gttttatgtt tttgacggac cagtcctaca ttgatgtttt 901 acctgagttc agagattctt accccattaa gtatgtccat gcctttgaaa gcaacaattt 961 tatttacttc ttgacggtcc aaagggaaac tctagatgct cagacttttc acacaagaat 1021 aatcaggttc tgttccataa actctggatt gcattcctac atggaaatgc ctctggagtg 1081 tattctcaca gaaaagagaa aaaagagatc cacaaagaag gaagtgttta atatacttca 1141 ggctgcgtat gtcagcaagc ctggggccca gcttgctaga caaataggag ccagcctgaa 1201 tgatgacatt cttttcgggg tgttcgcaca aagcaagcca gattctgccg aaccaatgga 1261 tcgatctgcc atgtgtgcat tccctatcaa atatgtcaac gacttcttca acaagatcgt 1321 caacaaaaac aatgtgagat gtctccagca tttttacgga cccaatcatg agcactgctt 1381 taataggaca cttctgagaa attcatcagg ctgtgaagcg cgccgtgatg aatatcgaac 1441 agagtttacc acagctttgc agcgcgttga cttattcatg ggtcaattca gcgaagtcct 1501 cttaacatct atatccacct tcattaaagg agacctcacc atagctaatc ttgggacatc 1561 agagggtcgc ttcatgcagg ttgtggtttc tcgatcagga ccatcaaccc ctcatgtgaa 1621 ttttctcctg gactcccatc cagtgtctcc agaagtgatt gtggagcata cattaaacca 1681 aaatggctac acactggtta tcactgggaa gaagatcacg aagatcccat tgaatggctt 1741 gggctgcaga catttccagt cctgcagtca atgcctctct gccccaccct ttgttcagtg 1801 tggctggtgc cacgacaaat gtgtgcgatc ggaggaatgc ctgagcggga catggactca 1861 acagatctgt ctgcctgcaa tctacaaggt tttcccaaat agtgcacccc ttgaaggagg 1921 gacaaggctg accatatgtg gctgggactt tggatttcgg aggaataata aatttgattt 1981 aaagaaaact agagttctcc ttggaaatga gagctgcacc ttgactttaa gtgagagcac 2041 gatgaataca ttgaaatgca cagttggtcc tgccatgaat aagcatttca atatgtccat 2101 aattatttca aatggccacg ggacaacaca atacagtaca ttctcctatg tggatcctgt 2161 aataacaagt atttcgccga aatacggtcc tatggctggt ggcactttac ttactttaac 2221 tggaaattac ctaaacagtg ggaattctag acacatttca attggtggaa aaacatgtac 2281 tttaaaaagt gtgtcaaaca gtattcttga atgttatacc ccagcccaaa ccatttcaac 2341 tgagtttgct gttaaattga aaattgactt agccaaccga gagacaagca tcttcagtta 2401 ccgtgaagat cccattgtct atgaaattca tccaaccaaa tcttttatta gtacttggtg 2461 gaaagaacct ctcaacattg tcagtttcct attttgcttt gccagtggtg ggagcacaat 2521 aacaggtgtt gggaaaaacc tgaattcagt tagtgtcccg agaatggtca taaatgtgca 2581 tgaagcagga aggaacttta cagtggcatg tcaacatcgc tctaattcag agataatctg 2641 ttgtaccact ccttccctgc aacagctgaa tctgcaactc cccctgaaaa ccaaagcctt 2701 tttcatgtta gatgggatcc tttccaaata ctttgatctc atttatgtac ataatcctgt 2761 gtttaagcct tttgaaaagc cagtgatgat ctcaatgggc aatgaaaatg tactggaaat 2821 taagggaaat gatattgacc ctgaagcagt taaaggtgaa gtgttaaaag ttggaaataa 2881 gagctgtgag aatatacact tacattctga agccgtttta tgcacggtcc ccaatgacct 2941 gctgaaattg aacagcgagc taaatataga gtggaagcaa gcaatttctt caaccgtcct 3001 tggaaaagta atagttcaac cagatcagaa tttcacagga ttgattgctg gtgttgtctc 3061 aatatcaaca gcactgttat tactacttgg gtttttcctg tggctgaaaa agagaaagca 3121 aattaaagat ctgggcagtg aattagttcg ctacgatgca agagtacaca ctcctcattt 3181 ggataggctt gtaagtgccc gaagtgtaag cccaactaca gaaatggttt caaatgaatc 3241 tgtagactac cgagctactt ttccagaaga tcagtttcct aattcatctc agaacggttc 3301 atgccgacaa gtgcagtatc ctctgacaga catgtccccc atcctaacta gtggggactc 3361 tgatatatcc agtccattac tgcaaaatac tgtccacatt gacctcagtg ctctaaatcc 3421 agagctggtc caggcagtgc agcatgtagt gattgggccc agtagcctga ttgtgcattt 3481 caatgaagtc ataggaagag ggcattttgg ttgtgtatat catgggactt tgttggacaa 3541 tgatggcaag aaaattcact gtgctgtgaa atccttgaac agaatcactg acataggaga 3601 agtttcccaa tttctgaccg agggaatcat catgaaagat tttagtcatc ccaatgtcct 3661 ctcgctcctg ggaatctgcc tgcgaagtga agggtctccg ctggtggtcc taccatacat 3721 gaaacatgga gatcttcgaa atttcattcg aaatgagact cataatccaa ctgtaaaaga 3781 tcttattggc tttggtcttc aagtagccaa aggcatgaaa tatcttgcaa gcaaaaagtt 3841 tgtccacaga gacttggctg caagaaactg tatgctggat gaaaaattca cagtcaaggt 3901 tgctgatttt ggtcttgcca gagacatgta tgataaagaa tactatagtg tacacaacaa 3961 aacaggtgca aagctgccag tgaagtggat ggctttggaa agtctgcaaa ctcaaaagtt 4021 taccaccaag tcagatgtgt ggtcctttgg cgtgctcctc tgggagctga tgacaagagg 4081 agccccacct tatcctgacg taaacacctt tgatataact gtttacttgt tgcaagggag 4141 aagactccta caacccgaat actgcccaga ccccttatat gaagtaatgc taaaatgctg 4201 gcaccctaaa gccgaaatgc gcccatcctt ttctgaactg gtgtcccgga tatcagcgat 4261 cttctctact ttcattgggg agcactatgt ccatgtgaac gctacttatg tgaacgtaaa 4321 atgtgtcgct ccgtatcctt ctctgttgtc atcagaagat aacgctgatg atgaggtgga 4381 cacacgacca gcctccttct gggagacatc atagtgctag tactatgtca aagcaacagt 4441 ccacactttg tccaatggtt ttttcactgc ctgaccttta aaaggccatc gatattcttt 4501 gctcttgcca aaattgcact attataggac ttgtattgtt atttaaatta ctggattcta 4561 aggaatttct tatctgacag agcatcagaa ccagaggctt ggtcccacag gccacggacc 4621 aatggcctgc agccgtgaca acactcctgt catattggag tccaaaactt gaattctggg 4681 ttgaattttt taaaaatcag gtaccacttg atttcatatg ggaaattgaa gcaggaaata 4741 ttgagggctt cttgatcaca gaaaactcag aagagatagt aatgctcagg acaggagcgg 4801 cagccccaga acaggccact catttagaat tctagtgttt caaaacactt ttgtgtgttg 4861 tatggtcaat aacatttttc attactgatg gtgtcattca cccattaggt aaacattccc 4921 ttttaaatgt ttgtttgttt tttgagacag gatctcactc tgttgccagg gctgtagtgc 4981 agtggtgtga tcatagctca ctgcaacctc cacctcccag gctcaagcct cccgaatagc 5041 tgggactaca ggcgcacacc accatccccg gctaattttt gtattttttg tagagacggg 5101 gttttgccat gttgccaagg ctggtttcaa actcctggac tcaagaaatc cacccacctc 5161 agcctcccaa agtgctagga ttacaggcat gagccactgc gcccagccct tataaatttt 5221 tgtatagaca ttcctttggt tggaagaata tttataggca atacagtcaa agtttcaaaa 5281 tagcatcaca caaaacatgt ttataaatga acaggatgta atgtacatag atgacattaa 5341 gaaaatttgt atgaaataat ttagtcatca tgaaatattt agttgtcata taaaaaccca 5401 ctgtttgaga atgatgctac tctgatctaa tgaatgtgaa catgtagatg ttttgtgtgt 5461 atttttttaa atgaaaactc aaaataagac aagtaatttg ttgataaata tttttaaaga 5521 taactcagca tgtttgtaaa gcaggataca ttttactaaa aggttcattg gttccaatca 5581 cagctcatag gtagagcaaa gaaagggtgg atggattgaa aagattagcc tctgtctcgg 5641 tggcaggttc ccacctcgca agcaattgga aacaaaactt ttggggagtt ttattttgca 5701 ttagggtgtg ttttatgtta agcaaaacat actttagaaa caaatgaaaa aggcaattga 5761 aaatcccagc tatttcacct agatggaata gccaccctga gcagaacttt gtgatgcttc 5821 attctgtgga attttgtgct tgctactgta tagtgcatgt ggtgtaggtt actctaactg 5881 gttttgtcga cgtaaacatt taaagtgtta tattttttat aaaaatgttt atttttaatg 5941 atatgagaaa aattttgtta ggccacaaaa acactgcact gtgaacattt tagaaaaggt 6001 atgtcagact gggattaatg acagcatgat tttcaatgac tgtaaattgc gataaggaaa 6061 tgtactgatt gccaatacac cccaccctca ttacatcatc aggacttgaa gccaagggtt 6121 aacccagcaa gctacaaaga gggtgtgtca cactgaaact caatagttga gtttggctgt 6181 tgttgcagga aaatgattat aactaaaagc tctctgatag tgcagagact taccagaaga 6241 cacaaggaat tgtactgaag agctattaca atccaaatat tgccgtttca taaatgtaat 6301 aagtaatact aattcacaga gtattgtaaa tggtggatga caaaagaaaa tctgctctgt 6361 ggaaagaaag aactgtctct accagggtca agagcatgaa cgcatcaata gaaagaactc 6421 ggggaaacat cccatcaaca ggactacaca cttgtatata cattcttgag aacactgcaa 6481 tgtgaaaatc acgtttgcta tttataaact tgtccttaga ttaatgtgtc tggacagatt 6541 gtgggagtaa gtgattcttc taagaattag atacttgtca ctgcctatac ctgcagctga 6601 actgaatggt acttcgtatg ttaatagttg ttctgataaa tcatgcaatt aaagtaaagt 6661 gatgcaacat cttgtaaaaa aaaaaaaaaa aaaaa

One example of a nucleic acid sequence for human MYH10 is available as NCBI accession number NM_(—)005964 (gi: 41406063). This sequence is recited below for easy reference as SEQ ID NO:149.

   1 actgaggcgc tggatctgtg gtcgcggctg gggacgtgcg cccgcgccac catcttcggc   61 tgaagaggca attgcttttg gatcgttcca tttacaatgg cgcagagaac tggactcgag  121 gatccagaga ggtatctctt tgtggacagg gctgtcatct acaaccctgc cactcaagct  181 gattggacag ctaaaaagct agtgtggatt ccatcagaac gccatggttt tgaggcagct  241 agtatcaaag aagaacgggg agatgaagtt atggtggagt tggcagagaa tggaaagaaa  301 gcaatggtca acaaagatga tattcagaag atgaacccac ctaagttttc caaggtggag  361 gatatggcag aattgacatg cttgaatgaa gcttccgttt tacataatct gaaggatcgc  421 tactattcag gactaatcta tacttattct ggactcttct gtgtagttat aaacccttac  481 aagaatcttc caatttactc tgagaatatt attgaaatgt acagagggaa gaagcgtcat  541 gagatgcctc cacacatcta tgctatatct gaatctgctt acagatgcat gcttcaagat  601 cgtgaggacc agtcaattct ttgcacgggt gagtcaggtg ctgggaagac agaaaataca  661 aagaaagtta ttcagtacct tgcccatgtt gcttcttcac ataaaggaag aaaggaccat  721 aatattcctg gggaacttga acggcagctt ttgcaagcaa atccaattct ggaatcattt  781 ggaaatgcga agactgtgaa aaatgataac tcatctcgtt ttggcaaatt tattcggatc  841 aactttgatg taactggcta tatcgttggg gccaacattg aaacatacct tctggaaaag  901 tctcgtgctg ttcgtcaagc aaaagatgaa cgtacttttc atatctttta ccagttgtta  961 tctggagcag gagaacacct aaagtctgat ttgcttcttg aaggatttaa taactacagg 1021 tttctctcca atggctatat tcctattccg ggacagcaag acaaagataa tttccaggag 1081 accatggaag caatgcacat aatgggcttc tcccatgaag agattctgtc aatgcttaaa 1141 gtagtatctt cagtgctaca gtttggaaat atttctttca aaaaggagag aaatactgat 1201 caagcttcca tgccagaaaa tacagttgcg cagaagctct gccatcttct tgggatgaat 1261 gtgatggagt ttactcgggc catcctgact ccccggatca aggtcggccg agactatgtg 1321 caaaaagccc agaccaaaga acaggcagat tttgcagtag aagcattggc aaaagctacc 1381 tatgagcggc tctttcgctg gctcgttcat cgcatcaata aagctctgga taggaccaaa 1441 cgtcagggag catctttcat tggaatcctg gatattgctg gatttgaaat ttttgagctg 1501 aactcctttg aacaactttg catcaactac accaatgaga agctgcagca gctgttcaac 1561 cacaccatgt ttatcctaga acaagaggaa taccagcgcg aaggcatcga gtggaacttc 1621 atcgatttcg ggctggatct gcagccatgc atcgacctaa tagagagacc tgcgaaccct 1681 cctggtgtac tggccctttt ggatgaagaa tgctggttcc ctaaagccac agataaaacc 1741 tttgttgaaa aactggttca agagcaaggt tcccactcca agtttcagaa acctcgacaa 1801 ttaaaagaca aagctgattt ttgcattata cattatgcag ggaaggtgga ctataaggca 1861 gatgagtggc tgatgaagaa tatggacccc ctgaatgaca acgtggccac ccttttgcac 1921 cagtcatcag acagatttgt ggcagagctt tggaaagatg tggaccgtat cgtgggtctg 1981 gatcaagtca ctggtatgac tgagacagct tttggctccg catataaaac caagaagggc 2041 atgtttcgta ccgttgggca actctacaaa gaatctctca ccaagctgat ggcaactctc 2101 cgaaacacca accctaactt tgttcgttgt atcattccaa atcacgagaa gagggctgga 2161 aaattggatc cacacctagt cctagatcag cttcgctgta atggtgtcct ggaagggatc 2221 cgaatctgtc gccagggctt ccctaaccga atagttttcc aggaattcag acagagatat 2281 gagatcctaa ctccaaatgc tattcctaaa ggttttatgg atggtaaaca ggcctgtgaa 2341 cgaatgatcc gggctttaga attggaccca aacttgtaca gaattggaca gagcaagata 2401 tttttcagag ctggagttct ggcacactta gaggaagaaa gagatttaaa aatcaccgat 2461 atcattatct tcttccaggc cgtttgcaga ggttacctgg ccagaaaggc ctttgccaag 2521 aagcagcagc aactaagtgc cttaaaggtc ttgcagcgga actgtgccgc gtacctgaaa 2581 ttacggcact ggcagtggtg gcgagtcttc acaaaggtga agccgcttct acaagtgact 2641 cgccaggagg aagaacttca ggccaaagat gaagagctgt tgaaggtgaa ggagaagcag 2701 acgaaggtgg aaggagagct ggaggagatg gagcggaagc accagcagct tttagaagag 2761 aagaatatcc ttgcagaaca actacaagca gagactgagc tctttgctga agcagaagag 2821 atgagggcaa gacttgctgc taaaaagcag gaattagaag agattctaca tgacttggag 2881 tctagggttg aagaagaaga agaaagaaac caaatcctcc aaaatgaaaa gaaaaaaatg 2941 caagcacata ttcaggacct ggaagaacag ctagacgagg aggaaggggc tcggcaaaag 3001 ctgcagctgg aaaaggtgac agcagaggcc aagatcaaga agatggaaga ggagattctg 3061 cttctcgagg accaaaattc caagttcatc aaagaaaaga aactcatgga agatcgcatt 3121 gctgagtgtt cctctcagct ggctgaagag gaagaaaagg cgaaaaactt ggccaaaatc 3181 aggaataagc aagaagtgat gatctcagat ttagaagaac gcttaaagaa ggaagaaaag 3241 actcgtcagg aactggaaaa ggccaaaaga aaactcgacg gggagacgac cgacctgcag 3301 gaccagatcg cagagctgca ggcgcagatt gatgagctca agctgcagct ggccaagaag 3361 gaggaggagc tgcagggcgc actggccaga ggtgatgatg aaacactcca taagaacaat 3421 gcccttaaag ttgtgcgaga gctacaagcc caaattgctg aacttcagga agactttgaa 3481 tccgagaagg cttcacggaa caaggccgaa aagcagaaaa gggacttgag tgaggaactg 3541 gaagctctga aaacagagct ggaggacacg ctggacacca cggcagccca gcaggaacta 3601 cgtacaaaac gtgaacaaga agtggcagag ctgaagaaag ctcttgagga ggaaactaag 3661 aaccatgaag ctcaaatcca ggacatgaga caaagacacg caacagccct ggaggagctc 3721 tcagagcagc tggaacaggc caagcggttc aaagcaaatc tagagaagaa caagcagggc 3781 ctggagacag ataacaagga gctggcgtgt gaggtgaagg tcctgcagca ggtcaaggct 3841 gagtctgagc acaagaggaa gaagctcgac gcgcaggtcc aggagctcca tgccaaggtc 3901 tctgaaggcg acaggctcag ggtggagctg gcggagaaag caagtaagct gcagaatgag 3961 ctagataatg tctccaccct tctggaagaa gcagagaaga agggtattaa atttgctaag 4021 gatgcagcta gtcttgagtc tcaactacag gatacacagg agcttcttca ggaggagaca 4081 cgccagaaac taaacctgag cagtcggatc cggcagctgg aagaggagaa gaacagtctt 4141 caggagcagc aggaggagga ggaggaggcc aggaagaacc tggagaagca agtgctggcc 4201 ctgcagtccc agttggctga taccaagaag aaagtagatg acgacctggg aacaattgaa 4261 agtctggaag aagccaagaa gaagcttctg aaggacgcgg aggccctgag ccagcgcctg 4321 gaggagaagg cactggcgta tgacaaactg gagaagacca agaaccgcct gcagcaggag 4381 ctggacgacc tcacggtgga cctggaccac cagcgccagg tcgcctccaa cttggagaag 4441 aagcagaaga agtttgacca gctgttagca gaagagaaga gcatctctgc tcgctatgcc 4501 gaagagcggg accgggccga agccgaggcc agagagaaag aaaccaaagc cctgtcactg 4561 gcccgggccc tcgaggaagc cctggaggcc aaggaggagt ttgagaggca gaacaagcag 4621 ctccgagcag acatggaaga cctcatgagc tccaaagatg atgtgggaaa aaacgttcac 4681 gaacttgaaa aatccaaacg ggccctagag cagcaggtgg aggaaatgag gacccagctg 4741 gaggagctgg aagacgaact ccaggccacg gaagatgcca agcttcgtct ggaggtcaac 4801 atgcaggcca tgaaggcgca gttcgagaga gacctgcaaa ccagggatga gcagaatgaa 4861 gagaagaagc ggctgctgat caaacaggtg cgggagctcg aggcggagct ggaggatgag 4921 aggaaacagc gggcgcttgc tgtagcttca aagaaaaaga tggagataga cctgaaggac 4981 ctcgaagccc aaatcgaggc tgcgaacaaa gctcgggatg aggtgattaa gcagctccgc 5041 aagctccagg ctcagatgaa ggattaccaa cgtgaattag aagaagctcg tgcatccaga 5101 gatgagattt ttgctcaatc caaagagagt gaaaagaaat tgaagagtct ggaagcagaa 5161 atccttcaat tgcaggagga acttgcctca tctgagcgag cccgccgaca cgccgagcag 5221 gagagagatg agctggcgga cgagatcacc aacagcgcct ctggcaagtc cgcgctgctg 5281 gatgagaagc ggcgtctgga agctcggatc gcacagctgg aggaggagct ggaagaggag 5341 cagagcaaca tggagctgct caacgaccgc ttccgcaaga ccactctaca ggtggacaca 5401 ctgaacgccg agctagcagc cgagcgcagc gccgcccaga agagtgacaa tgcacgccag 5461 caactggagc ggcagaacaa ggagctgaag gccaagctgc aggaactcga gggtgctgtc 5521 aagtctaagt tcaaggccac catctcagcc ctggaggcca agattgggca gctggaggag 5581 cagcttgagc aggaagccaa ggaacgagca gccgccaaca aattagtccg tcgcactgag 5641 aagaagctga aagaaatctt catgcaggtt gaggatgagc gtcgacacgc ggaccagtat 5701 aaagagcaga tggagaaggc caacgctcgg atgaagcagc ttaaacgcca gctggaggaa 5761 gcagaagaag aagcgacgcg tgccaacgca tctcggcgta aactccagcg ggaactggat 5821 gatgccaccg aggccaacga gggcctgagc cgcgaggtca gcaccctgaa gaaccggctg 5881 aggcggggtg gccccatcag cttctcttcc agccgatctg gccggcgcca gctgcacctt 5941 gaaggagctt ccctggagct ctccgacgat gacacagaaa gtaagaccag tgatgtcaac 6001 gagacgcagc caccccagtc agagtaaagt tgcaggaagc cagaggaggc aatacagtgg 6061 gacagttagg aatgcacccg gggcctcctg cagatttcgg aaattggcaa gctacgggat 6121 tccttcctga aagatcaact gtgtcttaag gctctccagc ctatgcatac tgtatcctgc 6181 ttcagactta ggtacaattg ctcccctttt tatatataga cacacacagg acacatatat 6241 taaacagatt gtttcatcat tgcatctatt ttccatatag tcatcaagag accattttat 6301 aaaacatggt aagacccttt ttaaaacaaa ctccaggccc ttggttgcgg gtcgctgggt 6361 tattggggca gcgccgtggt cgtcactcag tcgctctgca tgctctctgt catacagaca 6421 ggtaacctag ttctgtgttc acgtggcccc cgactcctca gccacatcaa gtctcctaga 6481 ccactgtgga ctctaaactg cacttgtctc tctcatttcc ttcaaataat gatcaatgct 6541 atttcagtga gcaaactgtg aaaggggctt tggaaagagt aggaggggtg ggctggatcg 6601 gaagcaacac ccatttgggg ttaccatgtc catcccccaa ggggggccct gcccctcgag 6661 tcgatggtgt cccgcatcta ctcatgtgaa ctggccttgg cgagggctgg tctgtgcata 6721 gaagggatag tggccacact gcagctgagg ccccaggtgg cagccatgga tcatgtagac 6781 ttccagatgg tctcccgaac cgcctggctc tgccggcgcc ctcctcacgt caggagcaag 6841 cagccgtgga cccctaagcc gagctggtgg aaggcccctc cctgtcgcca gccgggccct 6901 catgctgacc ttgcaaattc agccgctgct ttgagcccaa aatgggaata ttggttttgt 6961 gtccgaggct tgttccaagt ttgtcaatga ggtttatgga gcctccagaa cagatgccat 7021 cttcctgaat gttgacatgc cagtgggtgt gactccttca tttttccttc tcccttccct 7081 ttggacagtg ttacagtgaa cacttagcat cctgtttttg gttggtagtt aagcaaactg 7141 acattacgga aagtgcctta gacactacag tactaagaca atgttgaata tatcattcgc 7201 ctctataaca atttaatgta ttcagttttg actgtgcttc atatcatgta cctctctagt 7261 caaagtggta ttacagacat tcagtgacaa tgaatcagtg ttaattctaa atccttgatc 7321 ctctgcaatg tgcttgaaaa cacaaacctt ttgggttaaa agctttaaca tctattagga 7381 agaatttgtc ctgtgggttt ggaatcttgg attttccccc tttatgaact gtactggctg 7441 ttgaccacca gacacctgac cgcaaatatc ttttcttgta ttcccatatt tctagacaat 7501 gatttttgta agacaataaa tttattcatt atagatattt gcgcctgctc tgtttacttg 7561 aagaaaaaag cacccgtgga gaataaagag acctcaataa acaagaataa tcatgtgaa

One example of a nucleic acid sequence for human PFAAP5 is available as NCBI accession number AF530063 (gi: 33329092). This sequence is recited below for easy reference as SEQ ID NO:150.

   1 atgtcttatg gtgaaattga aggtaaattc ttgggaccta gagaagaagt aacgagtgag   61 ccacgctgta aaaaattgaa gtcaaccaca gagtcgtatg tttttcacaa tcatagtaat  121 gctgattttc acagaatcca agagaaaact ggaaatgatt gggtccctgt gaccatcatt  181 gatgtcagag gacatagtta tttgcaggag aacaaaatca aaactacaga tttgcataga  241 cctttgcatg atgagatgcc tggtaataga ccagatgtta ttgaatccat tgattcacag  301 gttttacagg aagcacgtcc tccattagta tccgcagacg atgagatata tagcacaagt  361 aaagcattta taggacccat ttacaaaccc cctgagaaaa agaaacgtaa tgaagggagg  421 aatgaggcac atgttctaaa tggtataaat gacagaggag gacaaaaaga gaaacagaaa  481 tttaactctg aaaaatcaga gattgacaat gaattattcc agttttacaa agaaattgaa  541 gagcttgaaa aggaaaaaga tggttttgag aacagttgta aagaatctga accttctcag  601 gaacaatttg ttccatttta tgagggtcat aataatggtc tcttaaaacc tgatgaagaa  661 aagaaagatc ttagtaataa agctatgcca tcacattgtg attatcagca gaacttgggg  721 aatgagccag acaaatatcc ctgtaatgga caagtaatac ctacattttg tgacacttca  781 tttacttctt tcaggcctga atggcagtca gtatatcctt ttatagtgcc ctatggtccc  841 cctcttccca gtttgaacta tcatttaaac attcagagat tcagtggtcc accaaatcca  901 ccatcaaata ttttccaagc ccaagatgac tctcagatac aaaatggata ttatgtaaat  961 aattgtcatg ttaactggaa ttgcatgact tttgatcaga acaatgaata tactgactgt 1021 agtgagaata ggagtagtgt tcatccctct ggaaatggct gcagtatgca agatcgatat 1081 gtgagtaatg gtttctgtga agtcagagaa agatgctgga aagatcattg tatggacaag 1141 cataatggaa cagacaggtt tgtgaaccag cagtttcaag aggaaaagtt aaataaattg 1201 cagaagttac ttattctttt aagaggtctg cctggttctg ggaaaacaac attgtctcga 1261 attctgcttg gtcagaatcg tgatggcatt gtgttcagca ctgatgacta ttttcaccat 1321 caagatgggt acaggtataa tgttaatcaa cttggtgatg cccatgactg gaaccagaac 1381 agagcaaaac aagctatcga tcagggaaga tctccagtta taatagataa cactaatata 1441 caagcttggg aaatgaagcc atatgtggaa gtggccatag gaaaaggata cagagtagag 1501 tttcatgaac ctgaaacttg gtggaaattt gatcctgaag aattagaaaa gaggaataaa 1561 catggtgtgt ctcgaaagaa gattgctcag atgttggatc gttatgaata tcaaatgtcc 1621 atttctattg taatgaattc agtggaacca tcacacaaaa gcacacaaag acctcctcct 1681 ccacagggga gacagaggtg gggaggctct cttggctcac ataatcgtgt ctgtgtcaca 1741 aataatcatt aa

One example of a nucleic acid sequence for human PGF is available as NCBI accession number NM_(—)002632 (gi: 56676307). This sequence is recited below for easy reference as SEQ ID NO:151.

   1 ctgctgtctg cggaggaaac tgcatcgacg gacggccgcc cagctacggg aggacctgga   61 gtggcactgg gcgcccgacg gaccatcccc gggacccgcc tgcccctcgg cgccccgccc  121 cgccgggccg ctccccgtcg ggttccccag ccacagcctt acctacgggc tcctgactcc  181 gcaaggcttc cagaagatgc tcgaaccacc ggccggggcc tcggggcagc agtgagggag  241 gcgtccagcc ccccactcag ctcttctcct cctgtgccag gggctccccg ggggatgagc  301 atggtggttt tccctcggag ccccctggct cgggacgtct gagaagatgc cggtcatgag  361 gctgttccct tgcttcctgc agctcctggc cgggctggcg ctgcctgctg tgccccccca  421 gcagtgggcc ttgtctgctg ggaacggctc gtcagaggtg gaagtggtac ccttccagga  481 agtgtggggc cgcagctact gccgggcgct ggagaggctg gtggacgtcg tgtccgagta  541 ccccagcgag gtggagcaca tgttcagccc atcctgtgtc tccctgctgc gctgcaccgg  601 ctgctgcggc gatgagaatc tgcactgtgt gccggtggag acggccaatg tcaccatgca  661 gctcctaaag atccgttctg gggaccggcc ctcctacgtg gagctgacgt tctctcagca  721 cgttcgctgc gaatgccggc ctctgcggga gaagatgaag ccggaaagga ggagacccaa  781 gggcaggggg aagaggagga gagagaagca gagacccaca gactgccacc tgtgcggcga  841 tgctgttccc cggaggtaac ccaccccttg gaggagagag accccgcacc cggctcgtgt  901 atttattacc gtcacactct tcagtgactc ctgctggtac ctgccctcta tttattagcc  961 aactgtttcc ctgctgaatg cctcgctccc ttcaagacga ggggcaggga aggacaggac 1021 cctcaggaat tcagtgcctt caacaacgtg agagaaagag agaagccagc cacagacccc 1081 tgggagcttc cgctttgaaa gaagcaagac acgtggcctc gtgaggggca agctaggccc 1141 cagaggccct ggaggtctcc aggggcctgc agaaggaaag aagggggccc tgctacctgt 1201 tcttgggcct caggctctgc acagacaagc agcccttgct ttcggagctc ctgtccaaag 1261 tagggatgcg gatcctgctg gggccgccac ggcctggctg gtgggaaggc cggcagcggg 1321 cggaggggat ccagccactt ccccctcttc ttctgaagat cagaacattc agctctggag 1381 aacagtggtt gcctgggggc ttttgccact ccttgtcccc cgtgatctcc cctcacactt 1441 tgccatttgc ttgtactggg acattgttct ttccggccaa ggtgccacca ccctgccccc 1501 cctaagagac acatacagag tgggccccgg gctggagaaa gagctgcctg gatgagaaac 1561 agctcagcca gtggggatga ggtcaccagg ggaggagcct gtgcgtccca gctgaaggca 1621 gtggcagggg agcaggttcc ccaagggccc tggcaccccc acaagctgtc cctgcagggc 1681 catctgactg ccaagccaga ttctcttgaa taaagtattc tagtgtggaa aaaaaaaaaa 1741 aaaaaaaaaa aaaaaaaa

One example of a nucleic acid sequence for human PIP3-E is available as NCBI accession number AJ310566 (gi: 18307480). This sequence is recited below for easy reference as SEQ ID NO:152.

   1 gtttaagtag aatcctcaag cttggcctca gagtactatg aggcttctga atccaggaat   61 aagactgctc ttggatttac tctctttgta ttgcatgtca aaggcaacag aactggacca  121 agaaaattca taactttttg cgtttgtttc tactaagatg acatcataca tggctattga  181 tggcagtgct cttgttccct tgcgtcagaa gcccaggagg aaaactcaag gttttctcac  241 gatgagtcgg aggaggatat cgtgtaaaga tctgggccat gctgactgcc aagggtggct  301 gtataagaaa aaggaaaagg gaagtttcct aagcaacaaa tggaaaaagt tctgggtgat  361 actgaagggg tcgtcactgt actggtatag caatcaaatg gcagagaaag ctgatggatt  421 tgtcaacctg cctgatttca ctgtggaaag agcatctgaa tgcaagaaaa agcatgcttt  481 taagatcagc catccacaga tcaagacctt ttattttgca gctgagaatg tgcaggaaat  541 gaacgtgtgg ttaaataaac ttggatcggc tgtaatccat caggaatcca ctacaaagga  601 tgaagaatgt tacagtgaaa gtgaacagga agatccagaa atagctgcgg agacaccacc  661 ccctcctcac gcttcccaga ctcagtcttt gactgcacag caggcatctt catcctcacc  721 cagcctgagt ggaacgtcgt attctttctc ttccctggaa aatacagtga agacacccag  781 cagttttcct tcctccttat ctaaagagag acaatccttg cctgacacag ttaacagttt  841 gtctgctgct gaagatgagg gacaaccaat aacgtttgct gtgcaagttc attcacctgt  901 accctcagag gcaggcatcc acaaggccct ggaaaacagt tttgtcacat cagaaagtgg  961 atttttgaac tctttatcta gtgatgatac ttcttcattg agtagcaatc atgaccatct 1021 tactgtccca gataagcctg ctggatcaaa gatcatggac aaagaagaga caaaagtgtc 1081 tgaagatgat gaaatggaga agctgtacaa atcattagag caagctagtc tatctcctct 1141 tggggaccga cgaccttcga ctaaaaagga gttgagaaaa tcctttgtta agcggtgtaa 1201 aaatccatct ataaacgaga aactccacaa aatccgaaca ttgaatagca cattaaagtg 1261 taaagaacat gatctggcca tgattaacca gttgctggat gacccgaagc tgacagccag 1321 gaaatacaga gagtggaaag tcatgaacac cctgctgatc caggacatct atcagcagca 1381 gcgggcttcg cctgcccctg atgacactga tgacaccccc caggaactca agaaatcacc 1441 ttcttctccc tctgttgaaa attccatttg agacaaagtc agggttttct cctcttatat 1501 tttatcacaa gcaactcttc aagatgttgc aaaagcttac atttttcctt aaaaggaaaa 1561 ctgaaaccca gtccttcaag catcagcttc ccatctaaag atgcacgtta gatgaagata 1621 at

One example of a nucleic acid sequence for human PKNOX2 is available as NCBI accession number NM_(—)022062 (gi: 116812643). This sequence is recited below for easy reference as SEQ ID NO:153.

   1 gtgtgaaggg ggggtccggg gggcgggtcc ctgtgccgct gacgtcccga gcagtgctgg   61 gaagtatagg ctgtgttgtc acgccggtgt cagtctgatg aagattggca tcaggtgaag  121 tctggagcag gacttctgag gctttctatc ctccatgctg ctcactagaa aaggggctgt  181 gaactgtgct ttggctctag cagacaggaa gaaattctgg cccagctgga agtagaaaga  241 ggggagtgag tctcctgagg accatctcag aggccccggg atcacccgaa cagtcctcca  301 tgtgaatcaa tcccatgatg caacatgcct ccccagcccc cgctctgacg atgatggcca  361 cgcagaatgt cccgccccca ccctaccagg acagcccaca gatgacggca accgcccagc  421 caccctccaa ggcccaggct gtccacatct ctgccccctc agctgctgcc agcacacctg  481 tgcccagtgc ccccatcgac ccccaggccc agctggaggc tgacaagcga gctgtataca  541 ggcaccctct tttcccgctc ctgacgctgc tgtttgagaa atgtgaacag gccacccagg  601 gctctgagtg catcacctcc gccagctttg atgtggacat cgagaacttt gtccaccagc  661 aggaacagga gcacaaaccc ttcttcagcg atgacccaga actggacaat ctgatggtga  721 aggcaatcca ggtcctgaga atccacctgc tggagctgga gaaagtcaat gaactctgca  781 aggacttttg taaccgttac atcacctgcc tcaaaaccaa gatgcacagc gacaacctgc  841 tcaggaatga tctagggggg ccctactccc ccaaccagcc ctccatcaac cttcactcac  901 aggacctcct gcagaattcc cccaattcca tgtccggagt ctccaataac ccccagggga  961 ttgtggtccc agcctcagcg ctccagcagg gcaacatcgc catgacaacc gtcaactcac 1021 aagttgtgtc aggtggagcc ttataccaac cggttaccat ggtaacctcc cagggtcagg 1081 tggtcaccca agcaatcccc cagggagcca tccagatcca gaacacacag gttaaccttg 1141 acctcacctc cctcctggac aatgaggata agaagtccaa gaacaaacga ggagtcttgc 1201 ccaagcatgc caccaatata atgcgttctt ggctcttcca gcatctcatg cacccctacc 1261 ccacggagga tgagaagagg cagatcgcag cccagaccaa cctcaccctc ctgcaagtaa 1321 acaactggtt catcaatgcc cggaggcgca tcctgcagcc catgcttgat gccagcaacc 1381 cagatcctgc ccccaaagcc aagaagatca agtctcagca ccggcccacc caaagattct 1441 ggcccaactc catcgctgcg ggggtgctgc agcagcaggg cggtgcccca gggacaaacc 1501 ccgatggttc catcaacttg gacaacctgc agtccctgtc ctcagacagt gccaccatgg 1561 ccatgcagca ggctatgatg gctgcacacg atgactcatt ggatgggaca gaagaagagg 1621 atgaggatga gatggaagag gaggaggagg aggagctgga ggaggaggtc gacgagctgc 1681 agacgacaaa tgtcagcgac ctgggcttgg aacacagtga ctccctggag tagtcgggca 1741 gcccagatgg cactgatcac tgagcaggag aggagtgtcg ccgggaggcc ttcagggtgg 1801 gggggaaggg gacatgggca ggaagcaccg agggagttgg gccctagctt ccccaaatca 1861 gtagcttgaa gaaaggcaaa ggagacacct gttccttccc aaccaccgag cttcaatgag 1921 gaccccagcc ccacttccct ggaactgccg aggactctgt ttggcggggc cagtcgagca 1981 gcctgtgtgg aaagacagga gtgagatctg gactcaccaa atccctgagg atagatggca 2041 cccatggccc ccacccacgg aaggacttga gttgtttaca agccctgcac tgaggcagat 2101 tggtgctgtt cgcagagtag gcctttgccc gggggcagac ttagaaggaa ggggagagac 2161 aaagggggac tgagtttcat ccccagaagt ttctcagctc ctttgacaga cattcaaggg 2221 caggagggag ccccaaagca taaccagtgg ccagaggagt gggagggcct gaggcatcac 2281 atcttgcaga tcagaatggg atggaatcca ccaggctcca gctcatccct ccaaggccct 2341 gtctctgcgc acagcaacca tggacatggg agaaagggat gggagccaca gtgcccttca 2401 ctctctcctg gaaaccaact gtaagctggt gggctcaacc tgtgggaggt taagaggagt 2461 cccttctggg ttgactccaa gagccaagga gatggcagac cctgggctag gaaccatatg 2521 gaggtgactt tgaggccaca gctgtcccta ggtgatcaca gaacttagct cctttaacaa 2581 caggacaatg gttttttacc ctagatgttc ccaccttcag tgctccacgc cctccataga 2641 ccttcagaga aggtgaaacc aggttatctg ggaatctttc cagcccgcag gtcgccacgg 2701 ccatcccttt gctcccagcc tggctccatc agcctccagc ttcctttctt cattctgtcc 2761 ttcagggaag gcagaagaaa cattggaaag catctagtcc agtgggaagc caggggttgg 2821 agaaggtgct acatccctct tcccatcaat atcctaaatg tgggggaggg cccagagaat 2881 ggcacccaag agcctgcggg gatgcccatc ccacacaccc cacccagctg ttctaaccct 2941 gctatccaca gccctggagg aactggggct cctggaagga ggaggaggct ctccactgtc 3001 caccctaaca cataccctcc cacccacctt ccagaccccc ttggttggca ccctctcctc 3061 cggttccctc tcaccccatg gctgtgaatg acaggacagg tcacacgtgt gttttccatt 3121 gggtttaatt taatggacgt gcagtttcat ttgtaaattg tgcattggcc acctccttca 3181 gtggcaggat gtgagtggct acctggctca actggagggg accccttggg ccctctgggg 3241 cttcccctcc cccacctggt tggggtagag caaaaggatg gtcactcttc cgaggtctcc 3301 ctgaaatgaa tgtatttctc ccccaaaaga gctgatattt aatgttttaa taaggatttt 3361 tgagaaacaa ataaccttat ttataatctg ggtgatccaa tcatttttta ctcccttttg 3421 atgccataca tagaggaaag tctagctttt ttggcgtgag acttttgcaa tgtgcagtgg 3481 gataaaatgc atttcctttt ctggttcgtt tttcttgtta acacgcgcac acagacacac 3541 acacacaccg ttccactcac cacctggaca ggcgtccccc agcacggaca cactggcaca 3601 caggtgccca catctcttcc tctcagcccc tccacctgcc taatgttatg caacctcctt 3661 ctgatgtatc caccaaacca gtactgaatg tggccgagac gttttcagta aatcttatta 3721 cctaccgtaa

One example of a nucleic acid sequence for human PRKACB is available as NCBI accession number NM_(—)182948 (gi: 46909585). This sequence is recited below for easy reference as SEQ ID NO:154.

   1 acacatgcat agctcttagc ttctgtgtaa gaagttgtga gctccttctg gaaacatttg   61 cagttacatt aagtaaagtg taaatgcaca tgaatggcag cttatagaga accaccttgt  121 aaccagtata caggtacaac tacagctctt cagaaattgg aaggttttgc tagccggtta  181 tttcatagac actctaaagg tactgcacat gatcagaaaa cagctctgga aaatgacagc  241 cttcatttct ctgaacatac tgccttatgg gacagatcaa tgaaagagtt tctagccaaa  301 gccaaagaag actttttgaa aaaatgggag aatccaactc agaataatgc cggacttgaa  361 gattttgaaa ggaaaaaaac ccttggaaca ggttcatttg gaagagtcat gttggtaaaa  421 cacaaagcca ctgaacagta ttatgccatg aagatcttag ataagcagaa ggttgttaaa  481 ctgaagcaaa tagagcatac tttgaatgag aaaagaatat tacaggcagt gaattttcct  541 ttccttgttc gactggagta tgcttttaag gataattcta atttatacat ggttatggaa  601 tatgtccctg ggggtgaaat gttttcacat ctaagaagaa ttggaaggtt cagtgagccc  661 catgcacggt tctatgcagc tcagatagtg ctaacattcg agtacctcca ttcactagac  721 ctcatctaca gagatctaaa acctgaaaat ctcttaattg accatcaagg ctatatccag  781 gtcacagact ttgggtttgc caaaagagtt aaaggcagaa cttggacatt atgtggaact  841 ccagagtatt tggctccaga aataattctc agcaagggct acaataaggc agtggattgg  901 tgggcattag gagtgctaat ctatgaaatg gcagctggct atcccccatt ctttgcagac  961 caaccaattc agatttatga aaagattgtt tctggaaagg tccgattccc atcccacttc 1021 agttcagatc tcaaggacct tctacggaac ctgctgcagg tggatttgac caagagattt 1081 ggaaatctaa agaatggtgt cagtgatata aaaactcaca agtggtttgc cacgacagat 1141 tggattgcta tttaccagag gaaggttgaa gctccattca taccaaagtt tagaggctct 1201 ggagatacca gcaactttga tgactatgaa gaagaagata tccgtgtctc tataacagaa 1261 aaatgtgcaa aagaatttgg tgaattttaa agaggaacaa gatgacatct gagctcacac 1321 tcagtgtttg cactctgttg agagataagg tagagctgag accgtccttg ttgaagcagt 1381 tacctagttc cttcattcca acgactgagt gaggtcttta ttgccatcat cccgtgtgcg 1441 cactctgcat ccacctatgt aacaaggcac cgctaagcaa gcattgtctg tgccataaca 1501 cagtactaga ccactttctt acttctcttt gggttgtctt tctcctctcc tatatccatt 1561 tcttcctttt ccaatttcat tggttttctc taaacagtgc tccattttat tttgttggtg 1621 tttcagatgg gcagtgttat ggctacgtga tatttgaagg gaaggataag tgttgctttc 1681 agtagttatt gccaatattg ttgttggtca atggcttgaa gataaacttt ctaataatta 1741 ttatttcttt gagtagctca gacttggttt tgccaaaact cttggtaatt tttgaagata 1801 gactgtctta tcaccaagga aatttataca aattaagact aactttcttg gaattcacta 1861 ttctggcaat aaattttggt agactaatac agtacagcta gacccagaaa tttggaaggc 1921 tgtagatcag aggttctagt tccctttccc tccttttata tcctcctctc cttgagtaat 1981 gaagtgacca gcctgtgtag tgtgacaaac gtgtctcatt cagcaggaaa aactaatgat 2041 atggatcatc acccagattc tctcacttgg taccagcatt tctgtaggta ttagagaaga 2101 gttctaagtt ttctaaacct taactgttcc ttaaggattt tagccagtat tttaatagaa 2161 catgattaat gaaagtgaca aattttaaat tttctctaat agtcctcatc ataaactttt 2221 taaaggaaaa taagcaaact aaaaagaaca ttggtttaga taaatactta tactttgcaa 2281 agtcaaaaat ggcttgattt ttggaaacaa tatagaggta ttcatattta aatgagggtt 2341 tacatttgtt ttgttttgta accgttaaaa agaagttgtt tccagctaat tattgtggtg 2401 tactatattt gtgagcctag ggtaggggca ctgctgcaac ttctgctttc atcccatgcc 2461 tcatcaatga ggaaagggaa caaagtgtat aaaactgcca caattgtatt ttaattttga 2521 ggtatgatat tttcagatat ttcataattt ctaacctctg ttctctcagt aaacagaatg 2581 tctgatcgat catgcagata caatgttggt atttgagagg ttagtttttt tcctacactt 2641 ttttttgcca actgacttaa caacattgct gtcaggtgga aatttcaagc acttttgcac 2701 atttagttca gtgtttgttg agaatccatg gcttaaccca cttgttttgc tatttttttc 2761 tttgctttta attttcccca tctgatttta tctctgcgtt tcagtgacct accttaaaac 2821 aacacacgag aagagttaaa ctgggttcat tttaatgatc aatttacctg catataaaat 2881 ttatttttaa tcaagctgat cttaatgtat ataatcattc tatttgcttt attatcggtg 2941 caggtaggtc attaacacca cttcttttca tctgtaccac accctggtga aacctttgaa 3001 gacataaaaa aaacctgtct gagatgttct ttctaccaat ctatatgtct ttcggttatc 3061 aagtgtttct gcatggtaat gtcatgtaaa tgctgatatt gatttcactg gtccatctat 3121 atttaaaacg tgcaagaaaa aaataaaata ctctgctcta gcaagttttg tgtaacaaag 3181 gcatatcgtc atgttaataa atttaaaaca tcattcgtat aaaatatttt aattttcttg 3241 tatttcattt agacccaaga acatgctgac caatgtgttc tatatgtaaa ctacaaattc 3301 tatggtagct ttgttgtata ttattgtaaa attattttaa taagtcatgg ggatgacaat 3361 ttgattatta caatttagtt ttcagtaatc aaaaagattt ctatgaattc taaaaaatat 3421 ttttttctat gaaattacta gtgcccagct gtagaatcta ccttaggtag atgatcccta 3481 gacatacgtt ggttttgagg gctattcagc cattccattt tactctctat ttaaaggccg 3541 tgagcaagct tgtcatgagc aaatatgtca agggagtcaa tttctgacca atcaagtaca 3601 ctaaattaga atatttttaa agtatgtaac attcccagtt tcagccacaa tttagccaag 3661 aataagataa aaacttgaat aagaagtaag tagcataaat cagtatttaa cctaaaatta 3721 catatttgaa acagaagata ttatgttatg ctcagtaaat aattaagaga tggcattgtg 3781 taagaaggag ccctagactg aaagtcaaga catctgaatt tcaggctgga aaactatcag 3841 tatgatctca gcctcagttc tcttgtctgt aaaatggaag aactggatta ggcagtttgt 3901 aagattcctc ctaactttca cagtcgatga caagattgtc tttttatctg atattttgaa 3961 gggtatattg ctttgaagta agtctcaata aggcaatata ttttagggca tctttcttct 4021 tatctctgac agtgttctta aaattatttg aatatcataa gagccttggt gtctgtccta 4081 attcctttct cactcaccga tgctgaatac ccagttgaat caaactgtca acctaccaaa 4141 aacgatattg tggcttatgg gtattgctgt ctcattcttg gtatattctt gtgttaactg 4201 cccattggcc tgaaaatact cattgtaagc ctgaaaaaaa aaatctttcc cactgttttt 4261 tctgcttgtt gtaagaatca aatgaaataa tgtatgtgaa agcaccttgt aaactgtaac 4321 ctatcaatgt aaaatgttaa ggtgtgttgt tatttcatta attacttctt tgtttagaat 4381 ggaatttcct atgcactact gtagctagga aatgctgaaa acaactgtgt tttttaatta 4441 atcaataact gcaaaattaa agtaccttca atggataaga caaaaaaaaa aaaaaaaaa

One example of a nucleic acid sequence for human PROS1 is available as NCBI accession number NM_(—)000313 (gi: 223671900). This sequence is recited below for easy reference as SEQ ID NO:155.

   1 tttggaaacg tcacactgtg gaggaaaagc agcaactagg gagctggtga agaaggatgt   61 ctcagcagtg tttactaggc ctccaacact agagcccatc ccccagctcc gaaaagcttc  121 ctggaaatgt ccttgttatc acttcccctc tcgggctggg cgctgggagc gggcggtctc  181 ctccgccccc ggctgttccg ccgaggctcg ctgggtcgct ggcgccgccg cgcagcacgg  241 ctcagaccga ggcgcacagg ctcgcagctc cgcggcgcct agcgctccgg tccccgccgc  301 gacgcgccac cgtccctgcc ggcgcctccg cgcgcttcga aatgagggtc ctgggtgggc  361 gctgcggggc gctgctggcg tgtctcctcc tagtgcttcc cgtctcagag gcaaactttt  421 tgtcaaagca acaggcttca caagtcctgg ttaggaagcg tcgtgcaaat tctttacttg  481 aagaaaccaa acagggtaat cttgaaagag aatgcatcga agaactgtgc aataaagaag  541 aagccaggga ggtctttgaa aatgacccgg aaacggatta tttttatcca aaatacttag  601 tttgtcttcg ctcttttcaa actgggttat tcactgctgc acgtcagtca actaatgctt  661 atcctgacct aagaagctgt gtcaatgcca ttccagacca gtgtagtcct ctgccatgca  721 atgaagatgg atatatgagc tgcaaagatg gaaaagcttc ttttacttgc acttgtaaac  781 caggttggca aggagaaaag tgtgaatttg acataaatga atgcaaagat ccctcaaata  841 taaatggagg ttgcagtcaa atttgtgata atacacctgg aagttaccac tgttcctgta  901 aaaatggttt tgttatgctt tcaaataaga aagattgtaa agatgtggat gaatgctctt  961 tgaagccaag catttgtggc acagctgtgt gcaagaacat cccaggagat tttgaatgtg 1021 aatgccccga aggctacaga tataatctca aatcaaagtc ttgtgaagat atagatgaat 1081 gctctgagaa catgtgtgct cagctttgtg tcaattaccc tggaggttac acttgctatt 1141 gtgatgggaa gaaaggattc aaacttgccc aagatcagaa gagttgtgag gttgtttcag 1201 tgtgccttcc cttgaacctt gacacaaagt atgaattact ttacttggcg gagcagtttg 1261 caggggttgt tttatattta aaatttcgtt tgccagaaat cagcagattt tcagcagaat 1321 ttgatttccg gacatatgat tcagaaggcg tgatactgta cgcagaatct atcgatcact 1381 cagcgtggct cctgattgca cttcgtggtg gaaagattga agttcagctt aagaatgaac 1441 atacatccaa aatcacaact ggaggtgatg ttattaataa tggtctatgg aatatggtgt 1501 ctgtggaaga attagaacat agtattagca ttaaaatagc taaagaagct gtgatggata 1561 taaataaacc tggacccctt tttaagccgg aaaatggatt gctggaaacc aaagtatact 1621 ttgcaggatt ccctcggaaa gtggaaagtg aactcattaa accgattaac cctcgtctag 1681 atggatgtat acgaagctgg aatttgatga agcaaggagc ttctggaata aaggaaatta 1741 ttcaagaaaa acaaaataag cattgcctgg ttactgtgga gaagggctcc tactatcctg 1801 gttctggaat tgctcaattt cacatagatt ataataatgt atccagtgct gagggttggc 1861 atgtaaatgt gaccttgaat attcgtccat ccacgggcac tggtgttatg cttgccttgg 1921 tttctggtaa caacacagtg ccctttgctg tgtccttggt ggactccacc tctgaaaaat 1981 cacaggatat tctgttatct gttgaaaata ctgtaatata tcggatacag gccctaagtc 2041 tatgttccga tcaacaatct catctggaat ttagagtcaa cagaaacaat ctggagttgt 2101 cgacaccact taaaatagaa accatctccc atgaagacct tcaaagacaa cttgccgtct 2161 tggacaaagc aatgaaagca aaagtggcca catacctggg tggccttcca gatgttccat 2221 tcagtgccac accagtgaat gccttttata atggctgcat ggaagtgaat attaatggtg 2281 tacagttgga tctggatgaa gccatttcta aacataatga tattagagct cactcatgtc 2341 catcagtttg gaaaaagaca aagaattctt aaggcatctt ttctctgctt ataatacctt 2401 ttccttgtgt gtaattatac ttatgtttca ataacagctg aagggtttta tttacaatgt 2461 gcagtctttg attattttgt ggtcctttcc tgggattttt aaaaggtcct ttgtcaagga 2521 aaaaaattct gttgtgatat aaatcacagt aaagaaattc ttacttctct tgctatctaa 2581 gaatagtgaa aaataacaat tttaaatttg aatttttttc ctacaaatga cagtttcaat 2641 ttttgtttgt aaaactaaat tttaatttta tcatcatgaa ctagtgtcta aatacctatg 2701 tttttttcag aaagcaagga agtaaactca aacaaaagtg cgtgtaatta aatactatta 2761 atcataggca gatactattt tgtttatgtt tttgtttttt tcctgatgaa ggcagaagag 2821 atggtggtct attaaatatg aattgaatgg agggtcctaa tgccttattt caaaacaatt 2881 cctcaggggg aacagctttg gcttcatctt tctcttgtgt ggcttcacat ttaaaccagt 2941 atctttattg aattagaaaa caagtgggac atattttcct gagagcagca caggaatctt 3001 cttcttggca gctgcagtct gtcaggatga gatatcagat taggttggat aggtggggaa 3061 atctgaagtg ggtacatttt ttaaattttg ctgtgtgggt cacacaaggt ctacattaca 3121 aaagacagaa ttcagggatg gaaaggagaa tgaacaaatg tgggagttca tagttttcct 3181 tgaatccaac ttttaattac cagagtaagt tgccaaaatg tgattgttga agtacaaaag 3241 gaactatgaa aaccagaaca aattttaaca aaaggacaac cacagaggga tatagtgaat 3301 atcgtatcat tgtaatcaaa gaagtaagga ggtaagattg ccacgtgcct gctggtactg 3361 tgatgcattt caagtggcag ttttatcacg tttgaatcta ccattcatag ccagatgtgt 3421 atcagatgtt tcactgacag tttttaacaa taaattcttt tcactgtatt ttatatcact 3481 tataataaat cggtgtataa ttttaaaatg catgtgaata tctttattat atcaactgtt 3541 tgaataaaac aaaattacat aatagacatt taactcttca aaaaaaaaaa aaaaa

One example of a nucleic acid sequence for human PSD3 is available as NCBI accession number NM_(—)015310 (gi: 117606359). This sequence is recited below for easy reference as SEQ ID NO:156.

    1 aacaaagagc acgcggcgct ggccgccggc actcgcgccc tgaggctgcg gccccggagc    61 gcccggcggc ggtttcggcg cgcggccggg ctggcgatgg aagatggaag gaaggagcgc   121 agcggcagag acatttgttt gggtgaacaa tgcatctgca cattcccaga gtgttgccaa   181 ggccaaatat gaatttttat ttggcagatc tgaagggaaa gctccagata ctagtgatca   241 tggaggaagc actttactcc caccaaatgt cacaaatgaa tttccagaat atgggaccat   301 ggaggaaggt ggagaaggcc taagggcttc tctggaattt gatggtgagg ctctgccatg   361 ccacccacaa gagcagcagg gtgtccagcc tcttactggc tgccactctg ggctcgacag   421 tgttacagaa ggaccaaaag atgtcagaga ggccccctct caaagtcatc tcaaggaaca   481 aagtttacag cccattgact ctttgatttc agctctgaaa gccacagaag ccagaatcat   541 ttccggaaca ttacaggcta caaaggtact ggaccaagat gctgtttcta gtttttcagt   601 tcagcaggtg gaaaaagagc tggacactgc cagtcgtaaa acacagagag tcaacaaaac   661 gctccctgct ggccaaaaaa atttaccaga aatacctctt tcagctgaag taacaacgga   721 ggaaagtttt tatttgagca tccagaaaga tctcaccgcg ctgttaactg gagacactca   781 ggcagagatt tcccagataa tgaataatgg gaggaaaggg gctgtctgtg tgcaggagcc   841 atcttgtcct ttggcctccc tcgggagctc agcagtgacc tgccactctg caggcagtgt   901 tggtttcttg aaagagcaga ggtctgctct tgggagagag cacccagggg gatgtgatcg   961 aagcagctcc atgggacgcc caggccgggt caaacatgtg gaatttcaag gagtggaaat  1021 actgtggaca ggaggagaca agagagagac ccagcatcct atagattttg agacatcact  1081 gcaaagaaca gcctctcctg acagcaaaga gtcttccaaa gtgccacgcc atctcatctc  1141 atcagctggt ttgtgtaatt caagtagttt aactgagaat gtttgggatg aatcctggaa  1201 agctccttca gagaggcctg gcactagctc ggggacattt tcccctgtgc gtcttgatga  1261 gagtggagag gatgaagtct tcctacagga aaacaaacag catcttgaga agacacctaa  1321 accagagaga gacagggaaa ggatcagcga acaagaggag cacgttaagg gggaagatga  1381 agacatcctt gggcctggat atacggagga ctccaccgac gtgtacagct cccagtttga  1441 aaccattttg gacaacactt ctttatacta cagtgcagag tccctggaga cattatactc  1501 agagcctgat agctatttta gctttgaaat gcccctcact ccaatgatac aacagcgcat  1561 taaagaaggt ggtcagttct tggagaggac atcaggggga ggacatcagg atatcctgag  1621 tgtgtctgca gatggtggca tcgtgatggg ctattctagt ggcgtcacca atgggctgaa  1681 tgatgccagc gactccatct acacgaaagg caccccggag attgctttct ggggaagcaa  1741 tgctggggtg aaaacaacac ggctagaagc tcattctgaa atggggagca ctgaaatttt  1801 ggaaaaggag accccagaaa atctcagtaa tggtaccagc agcaatgtgg aagcagccaa  1861 aaggttggcc aaacgccttt atcagctgga cagattcaaa agatcagatg ttgcaaaaca  1921 ccttggcaag aacaacgaat ttagcaaact agttgcagaa gaatatctga agttttttga  1981 ttttacagga atgacgctgg atcagtcact caggtatttc tttaaagcat tctctcttgt  2041 gggagaaact caagaacgag agagagtttt aatacacttc tccaatagat atttttattg  2101 taacccagat accattgctt cacaagatgg agtccattgc cttacctgtg caataatgct  2161 tcttaatacc gatctacatg gccacaatat tggaaagaag atgacctgtc aggagttcat  2221 tgcaaatctg caaggggtaa atgagggtgt tgatttctcc aaggatctgc tgaaagctct  2281 gtacaactca atcaagaatg agaagcttga atgggcagta gatgatgaag agaaaaaaaa  2341 gtctccctca gaaagtactg aggagaaagc taacggaaca catccaaaga ccatcagtcg  2401 tattggaagt actactaacc catttttgga cattcctcat gatccaaatg ctgctgtgta  2461 caaaagtgga ttcttggctc ggaaaattca tgcagatatg gatggaaaga agactccaag  2521 aggaaaacga ggatggaaaa ccttttatgc tgtactgaag ggaacagttc tttacttgca  2581 aaaggatgaa tacaagccag aaaaggcctt gtctgaagag gacttgaaaa acgctgtgag  2641 tgtgcaccac gcattggcat ccaaggccac ggactatgag aagaaaccaa acgtgtttaa  2701 acttaaaact gccgactgga gggtcttgct ttttcaaact cagagcccag aggaaatgca  2761 agggtggata aacaaaatca attgtgtggc agctgtattt tctgcaccac catttccagc  2821 agcaatcggc tctcagaaga agtttagccg cccacttctg cctgccacta caacaaaact  2881 gtctcaggag gagcaactga agtcacatga aagtaagctg aagcagatca ccaccgagct  2941 ggccgagcac cgctcatatc cccccgacaa gaaggtcaaa gccaaggacg tcgatgagta  3001 caaactgaaa gaccactatc tggagtttga gaaaacccgc tatgaaatgt atgtcagcat  3061 tctcaaggaa ggaggcaaag agctactgag taacgatgaa agcgaggctg caggactgaa  3121 gaagtcgcac tcgagtcctt cgctgaaccc ggatacttct ccaatcactg ccaaagtcaa  3181 gcgtaacgtg tcagagagga aggatcaccg acctgaaaca ccaagcatta agcaaaaagt  3241 tacttagagt ccatctgcgg ccaggaagtg ctggtcatgg agcaaaatag ggtttttcaa  3301 gatctttctg gtaatccgtg aatatattta aaaaaaaaaa gtctgtgaca aaacggtgca  3361 ttagtaattt tttctattgt atatttttgt tagtttctgt acagattgtc tttgctcttg  3421 atttcttttg ctttgatgat ttttgcaact tgatagctaa tgcacctttt ctgtgaggag  3481 gaggggatcg tgatttcaga atgaattatg tatcccttct cttttggttt tctcttgttt  3541 gcagtctgct cagttgtttt atgtattctc atatcaactg ttaaactttt ttttaaggtt  3601 aaagaattta atccattgtg aaacacttaa ctggacaaac tgtagtttta gtaaattcta  3661 gctggagtta atatacgcct ttatatgtga aatcttgccc agtcacagag gtagaattga  3721 gcactcacag atgctccagt aagaatcaca gtgctgggaa tctagttgct ccaatatgag  3781 gcagcttcat gtgcagctta gcacttgttg ttgagatcgg accctgctgg aagcagggaa  3841 aagaagcgtg aagatcgtag gattgagaac ttagggaagc acattagctt gcttgaagtg  3901 ctgattccat ttcagccaag caagggaaag aggaagtgga gtcattttgc ctttgaaggc  3961 tgaggaaaga ttgataccca gttaattttg tttgctaaag gatgggggca ataatcggcc  4021 cttgaggagc tgcagcagta ggcatgtgct cagtctgcag gaattgttac ctcactccca  4081 cagggtctag actagaaatc catcatctct atcgttgata tccttccatc caggaataga  4141 tttttcttac tctacatatg tgtgtgtgcg tgcgtgtgtg tgcgtgtgtg ggcatggggt  4201 tgtgtcctgg ttgtgatatt gaggtcttcc ttcctaacaa attaatacta aaatgaaaca  4261 gcttttcttg tgtccttaag acaaaataag gaaggaaaac gtagctgcag ttgtccacga  4321 tggatattgg ttctttaaaa tatatctgaa agtagtagtc agaatgaatt atggttggaa  4381 aactgaggaa tcttctggtt gcaggtgcaa agtgactttg tttattcttg tctcagtctc  4441 cttgatagcc acttcactct gctactactc aactttctcc taaaaatact tcatctattt  4501 tcagtccttt ctttctgtct actcaaaatg gttctattaa ctttgcagtc atgagcttgt  4561 tccagttaca gtccctttga agttcagggt gataaacaga atattcttct gtagaggaag  4621 agaaaggagt gaaagtttag cccactgaga cctagagctt tgtgatttcc taaccttgaa  4681 actctgtaat ccctaaagtt aaaatctccg caagtggcac aacttcagaa ctaatagtat  4741 cactttgatt tttctttttc ctcccttaga aagtttctct agttctatag tttatttgtt  4801 gaaggtacta tgaccaaaga atcagctgct ctacaggaat agcatggttc cagtgaatta  4861 gagaaaacct gctgtaaagc catggtagtg tctaagtggt atgttattat gatgtactag  4921 catttattta cagaattatt tattaacgtt tacttccttc ccctctgtaa atgtccatga  4981 ctattgccca gagaaggctt acccctctct agggttgcag ttgctttctt tgtaataagt  5041 attttgccac acctgtaaaa aaaaaaacct cacttttaac tctctgcctt gtttgggtaa  5101 aggcagtaac taagtttatg tttcagaact gcaaaacaaa caggatagtt accaatatgg  5161 cccatgtatc agattgattt ttgtagcctc tcactgaatc caacatatcc acaagcaagt  5221 tatctgtctt tctacctgat aatctaaatt atcaggatat ttgttttctg cctaaatgtt  5281 tatactaagc cgaggggaga gaggtaccta gaccatgtca tctacaagct tcagtaacta  5341 aagaaaaagg aacttccctg agtggcttga atgtgtttgc ccacagtcta tatctatgta  5401 tatagaatgt ctgtatgtat tttacttatt taatatacat tgaatggtac cttgctacag  5461 tatttctgac atttagagta gtgttgaaat actcggctag catcagcacc actatagcac  5521 tgtccgtgtc atatgagtca ctaatattaa ctccagggac ttctggatag gctaatagat  5581 cattggatac gaagggctct tttgaagctt cagtatacca tgtttgcata gtttatcttt  5641 aaaaacaact ttaaaggttc ttttgtgagc caggatctca gactgccgta gcatgatgct  5701 gtccatcttt agcgcatggg ctgagaacac ctcttccctg aggcttctga aggttgctgt  5761 ctgtcatgag tgcatgaagg aggccaagag tttatgctat gggaggaaac agtcactgat  5821 ttgcctagat tctgagagtc tggcccatag ccaaccacat tttcctttgg gataatttat  5881 ttcctgtggc atctagccag aagaaattga ggatgtttcc tttcacagct gctccaagcc  5941 tgttgcccaa ttcacggtac aagggagcac cccttccctt tcctctgaag gtacgccacc  6001 cacctccgtc gcccacctca gcgcccagga gccttgggac ttccttccat atgataaatc  6061 attcttcttc acgtcaatac acttcatatt aatttctagt acagaaaatc ttgacagcta  6121 tcagaatgcc ttggtcatag tgttgttgca aaattgacca tacaggtggc ccatgtataa  6181 aatctgaatt ttaggggttt gtccccacct cgcatgctgg cttttacagg gaggtgtctg  6241 ggattcctca ttagcaatca aaacttaatt actgggatgc agagtcctta ctttatcgcc  6301 agcccgtagg catttctgaa gtgcactttt ttgaaacatc attttgctaa ctctcagcag  6361 tgtctaatta aactgagcaa tacttttgtg aattttaatt aatctcagca aaaccatgat  6421 gggagagagt cctctgatgg aaatgtagtc cctggattat gtgtaacctt tttattcctc  6481 ttagatgcag aggatagaaa gcattttttg gtgcagtggt cttgtggcaa acacaagacc  6541 ctctatgcgt ctccaactgt tatcctaatc tagaaaatga ggactggccc ctgggcaaaa  6601 gtgacatgag gaatttactc tggaagagga aaatctgggt ggctttccaa ggctaagata  6661 ggtttgtatt tcaccctgtg gccaagctac agaacttctg agattgtgga agaatttttg  6721 caaccagcag ggaaagaggc ctcttactgc ctaaacacaa agttacactg agcttttcta  6781 ctgtcctttg cctattgctc cctctatcat gtaaagatct gggaaggatg agaggcaggg  6841 cctgcttgtc atgagctgca ctcttttctt tttaactaat cattgacaat tggaagaaaa  6901 ttgacgttaa agaagtttct ccattgtctt actaacaaaa ccttttgggt ttcattaatt  6961 gtccttgaaa ttgagttcct ttggcatttt tccttgcagt catcagttaa gcatgttgca  7021 tcctgaattc acagaagttt agctttgcag gtttgaatct ctgtaattta actcccgtgg  7081 acttggtcga gttttcagca ggttgggagc cacctctctt catttcagca gtgagtcatc  7141 ccttgacttt tcaaatgaca gaattttttc caattgtaaa attagcactg taaaacaaag  7201 aaccaaagtg gcatcctaag agttgttaaa cctgaagtct agtttatgag gaattgtcca  7261 agttggagtt taaatagtat ctgcttttgt ctcaaagcat ctaagttatt ctgacagaaa  7321 atggtaagtc agctttgcag gcagatgcgc ctctgggcct cctaccttgc tccacagctt  7381 tctggccatc ttgtctccca ggccatgcca ctgctctgcc acatgtcagc aaatttcttt  7441 ccaccagtct tatagcatct tacatgatca aatcatcaca gaataacccc gtgatagatt  7501 attgatagca atagagaggg gctttgtcac tgatttttct ctcagattcc ttttccatct  7561 ctcatccata aaggaaggac tgaaatccaa aggcattctc cttttgtacc tacagtatcc  7621 agaacccacg tgggcagcct tctgcttatg acaataattg gcccattgca tgcagagaga  7681 atgtcttcat agagagaatg tcattaaata cttgaatctg catgacagtt tgacttgaat  7741 gcaacagcag gaaaattttg caagttacat aattgtatat acagtaggtt ttcttaagtc  7801 tcttcggttc atcctttgta atttgtgtgt gtatctgtag tattgcaggc ttttggagac  7861 tattcttaca ggcagtatgt cagtcatcaa agaaaatgct gtcacctgcc attgttgtat  7921 ttgtgggtat ttatagttgt atgtatgtaa atgcatcagt gtgtagattg catatcagtg  7981 tatggtacat gtacatcaaa attatttttg tccttaatca gtgtgatatg aaaagcaagt  8041 acaacctcat aggactgatt atataatgaa gttgttgaga gtatatatag tggtattgtt  8101 ttattaaact taaactcaaa taatattttg attaaaattt ttaataagac tttatgctag  8161 aaaattcttt gagctttgaa tcaccagggc aaaaatgact ttcaactaac cttgtgaatc  8221 ttttgcagtg tactgtgtgc aataccaagg gcatagctcc ctgtaatttg ggaaatacag  8281 aaagaaaaga aaaaaaaaaa aaaaggcagc ctgtgcagtc ttagtaactt tagtattaag  8341 agcacttaaa gtcaaactga caattttggg cttattacaa aatgtgatgc tttaaagcac  8401 acgttcttta ttgttgttgt aattagtcca taaaaaatat agctttcgga agaattaagt  8461 acccaccata tcatttatgt atttgtgtat gttttacggg agatcaaacc actctcgtgg  8521 tgccgcatcc gtactcgctt gacttggaag aaatatcaca agcactaaag tatatcaggg  8581 catcccagga ttgggtactg tatcctaggt ttgcagttgc agaaattagc atctagtgtc  8641 acaggtaaaa gaatttcagg accaggttta aactttattt taaatatttt tatacttagg  8701 tctctttttc ctgcctctcc ccaaagaaga gccactggcc ttagttgttt gagcttactg  8761 cttatattat agagtgtaaa taggtaacta gagactaaaa ttttattaac cagcatgttt  8821 ggtatattta aagcagtgac tgagtgtgtt tgagtgagtg gctgagtgca gtgtcttttg  8881 tttaaacaca ctgcctcgtg tctttgtagc tgattcagag agtttgaatt gtggggtggg  8941 agactaactt cagctccagg ctgcagtaat gtgttggtag ttacacttga ggcatttttt  9001 tgttgttgtt aattaactct atagtctcaa actatttttg caaatatatc atttttccta  9061 attggttctt gacgtgcagt ggactggctc tgtgaatgat tggcagggtc ttagttttgc  9121 gagagtattt ccttctaaga attattgtga tctgcagaaa cagccatttg attcaaaaat  9181 catgtagaaa aggagtagga gaagcaaaac gtttcatttt tgggccttaa ccatttgaaa  9241 tgtttggact ttaaacataa agccatggag tttataaagc caagtaacca tttgatatgg  9301 ataataatat ctactctaga gagagtatat atatgcacat tgatttttaa tgctgttaag  9361 atacttttgt aaaactgtag gaacaagagt aattagacca aattgaagct taggggacag  9421 taaagtggtt gctttccatt tagggtaacc atgcatgtgg ttagtcctct cctcctgaga  9481 ttcagaacca gttgactgtc cccttaggtg tataaggaga aaagttgaca tgtctgggac  9541 ctctgacatg tgtacacatg cttgcacaca tgcacacaca gtgaatgttt taagttatac  9601 aaacataaga ccttaagatg caaagagcca gaatattcta aagaggtgat gaacagaggg  9661 ggtggaaact gcatcacaga tgttttccaa gggccagggt ggaatctgag ctctagtgtc  9721 tgactttgag atgcattata tttttaacac ataaatgagg ggatccatat cacattcttt  9781 cttgtggacc accaaattga aggctttctt gtaattcaca agcagcagct ctccagcatc  9841 tctccgtagc ctgggtgaag tcccagaagc tggtgtgcat cattttccaa ggtggcagag  9901 ctgcttgctc tgcagatcat tcctttgaga gaggagtaca agtgaagaaa caaggaggca  9961 cttcctgtag gagcactgat gtgccttgtc cacactcccc tctgagcttt actggtaaga 10021 gagctccgac tgaacatgct gagcagttga gcacttttcc atcagcaaca acagcgagga 10081 tggaaatgga aaggaaccga actaaaatgc atttcccttt gcagggcaga gagctaagct 10141 cttaggaata gtgttataga aataagcacc ctaacttcaa ttcctgaaaa tgttggttaa 10201 tggagagaat tttggagttt cacttaatat tttcccatcg gtcgccataa ataagtcttc 10261 aggcgctcct agaagagtcc cagcccaagg ctcgattaag gaccacactg caggtctgag 10321 gctcactgct ctgagtcctg aacaccagag ccctgcagag agtggtgata acacatcatc 10381 tctgcaaaga ggaacctctc ccccggccgc cacttcactc aggcttctac tgagcagcaa 10441 ggacagcctg ggtttcaaat gccacttccc ctgctttagg gatccaggtg tcctgatagc 10501 gtgaccctgc tgaggcaagg tatcaactcc gagagtgact gagtcactga gcgtggcaca 10561 tgaacaaacg tcatgacaaa gattctctga gtgaagttaa caccacgtat tttacctttg 10621 caaaaaacaa actggcaccc tgagttctaa ctacggacgg acgatatctt tgcctccaca 10681 cccagattcc tggaaatggc taacgtttcc tttctagggg aagggtcgag gaatactcaa 10741 gtgctagctt agcagctttg ttcagtccag atcagagctg ttaggtaaag gcctaaccac 10801 ctccctgcag tctcttatat ctcaagcttt aggaacccat ttctaaatgt acactagcgg 10861 agaatttata ttgtcagcct tgattaccat aggacaggca gaaaggcgat aatttgtatc 10921 ttttaatata aaagaagctt ttaacttttc cagcctatta taataactga gttatattca 10981 ctgtggctca aactaattgg cattgtggaa catttcttta ccttcaaagt tttctccacc 11041 aatcatttca gttctattgc agtcctggtg ccatatgtcc cctgcaaatt gtgaaagtaa 11101 ttagtgacaa aatagcagcc tgctcctttt caatggcgaa actgtcggca ttagcagttt 11161 tgggtaagct ggcggtacta taacacgtac tggaaacctg ttcctcatca ccacctacca 11221 gattctggaa atgccgtctt ctagaaaacg atggcgtttg tggtggtctt cttttgaaag 11281 gaacagtaat ttgtgtggat attgttaaag tgtttaaaga atattttgac aattaagttt 11341 acattttaca attgctttat tttttattaa aatagttgta tataaatatt accctatttc 11401 actgttgttc aagtaaatct aaaccttgta gacaagtgag tcatctgata tgtatagaag 11461 ctgtgatata tagagtacat ttattgtgta aatgtttatg aatataattg ttcctgtgtt 11521 tttataagtt ggggatattt tgttgtttta cggcaacaaa atttattgca tttaaatggt 11581 ttttatgtaa tagaaatcac gcaaaatagt gaaggattta aaatatgtat atgatacatg 11641 taaatgtaca aactttagaa agaaataaat ccaacaaatt tcaatca

One example of a nucleic acid sequence for human QPCT is available as NCBI accession number NM_(—)012413 (gi: 68216098). This sequence is recited below for easy reference as SEQ ID NO:157.

   1 ggcgatggga aggcgggcgc agtcgaccca agggtggaga agagggaagg cgaaggacgc   61 gcgttcccgg gctcgtgacc gccagcggcc cggggaaccc gctcccagac agactcggag  121 agatggcagg cggaagacac cggcgcgtcg tgggcaccct ccacctgctg ctgctggtgg  181 ccgccctgcc ctgggcatcc aggggggtca gtccgagtgc ctcagcctgg ccagaggaga  241 agaattacca ccagccagcc attttgaatt catcggctct tcggcaaatt gcagaaggca  301 ccagtatctc tgaaatgtgg caaaatgact tacagccatt gctgatagag cgatacccgg  361 gatcccctgg aagctatgct gctcgtcagc acatcatgca gcgaattcag aggcttcagg  421 ctgactgggt cttggaaata gacaccttct tgagtcagac accctatggg taccggtctt  481 tctcaaatat catcagcacc ctcaatccca ctgctaaacg acatttggtc ctcgcctgcc  541 actatgactc caagtatttt tcccactgga acaacagagt gtttgtagga gccactgatt  601 cagccgtgcc atgtgcaatg atgttggaac ttgctcgtgc cttagacaag aaactccttt  661 ccttaaagac tgtttcagac tccaagccag atttgtcact ccagctgatc ttctttgatg  721 gtgaagaggc ttttcttcac tggtctcctc aagattctct ctatgggtct cgacacttag  781 ctgcaaagat ggcatcgacc ccgcacccac ctggagcgag aggcaccagc caactgcatg  841 gcatggattt attggtctta ttggatttga ttggagctcc aaacccaacg tttcccaatt  901 tttttccaaa ctcagccagg tggttcgaaa gacttcaagc aattgaacat gaacttcatg  961 aattgggttt gctcaaggat cactctttgg aggggcggta tttccagaat tacagttatg 1021 gaggtgtgat tcaggatgac catattccat ttttaagaag aggtgttcca gttctgcatc 1081 tgataccgtc tcctttccct gaagtctggc acaccatgga tgacaatgaa gaaaatttgg 1141 atgaatcaac cattgacaat ctaaacaaaa tcctacaagt ctttgtgttg gaatatcttc 1201 atttgtaata ctctgattta gtttaggata attggttcta gaattgaatt caaaagtcaa 1261 ggcatcattt aaaataatct gatttcagac aaatgctgtg tggaaacatc tatcctatag 1321 atcatcctat tcttatgtgt ctttggttat cagatcaatt acagaataat tgtgttgtga 1381 tattgtgtcc taaattgctc attaattttt atttacagat tgaaaaagag ggaccgtgta 1441 aagaaaatgg aaaataaata tctttcaaag actcttttag ataaacacga tgaggcaaaa 1501 tcaggttcat tcattcaacg atagtttctc aacagtactt aaatagcggt tggaaaacgt 1561 agccttcatt ttatgatttt ttcatatgtg gaaatctatt acatgtaata caaaacaaac 1621 atgtagtttg aaggcggtca gatttctttg agaaatcttt gtagagttaa ttttatggaa 1681 attaaaatca gaattaaatg ctaaaaaaaa aaaaaaaaa

One example of a nucleic acid sequence for human RAB27A is available as NCBI accession number NM_(—)004580 (gi: 34485707). This sequence is recited below for easy reference as SEQ ID NO:158.

   1 gttttgaaag ttgatggagc gaactgcttt tccaaagact cttttgaaaa actttttaag   61 taggccattc tgactttaac atttctcttt gtcttaacat tagacaaaaa gtaaccttcc  121 tgaagaggac atgtgattgg aagttgtcaa ttgttgaagc attggtaact ccagtctcta  181 acgttttaga aaatcataac aagcggttct ctaccctgta aaggtgaact actgagttct  241 tcattatgtc tgatggagat tatgattacc tcatcaagtt tttagctttg ggagactctg  301 gtgtagggaa gaccagtgta ctttaccaat atacagatgg taaatttaac tccaaattta  361 tcacaacagt gggcattgat ttcagggaaa aaagagtggt gtacagagcc agtgggccgg  421 atggagccac tggcagaggc cagagaatcc acctgcagtt atgggacaca gcagggcagg  481 agaggtttcg tagcttaacg acagcgttct tcagagatgc tatgggtttt cttctacttt  541 ttgatctgac aaatgagcaa agtttcctca atgtcagaaa ctggataagc cagctacaga  601 tgcatgcata ttgtgaaaac ccagatatag tgctgtgtgg aaacaagagt gatctggagg  661 accagagagt agtgaaagag gaggaagcca tagcactcgc agagaaatat ggaatcccct  721 actttgaaac tagtgctgcc aatgggacaa acataagcca agcaattgag atgcttctgg  781 acctgataat gaagcgaatg gaacggtgtg tggacaagtc ctggattcct gaaggagtgg  841 tgcgatcaaa tggtcatgcc tctacggatc agttaagtga agaaaaggag aaaggggcat  901 gtggctgttg agaagtcaag taagcgacat agtagttcag gtggcccatg cctgggatct  961 tctctatgat tgatacatgg cacagtgaga gattaatggg cattgtgtac aaattgcttc 1021 tcaccatccc cattagacct acgaataaag catccggttc taaaattaat ttgttgcagc 1081 tttgtaaata tttctttaag attcagcctg agagttagga gaaatatttc agagccaaaa 1141 gtgccttata caaccttagc ctattatagt aaatcattca aggattcaga attttgcagt 1201 cacagaagag tgtatttatt atgtagaatg aatgagggta ctgtcacctg ccttaatgta 1261 ggtaggccca gagtcttaca tttaagatct tacatgcagt tataaaaccg ccacagtctt 1321 caatccagat ttgaagactc atgccatagg tgacattcta aaataccatt aaagccactt 1381 aaatgttaaa taagaatata catgcacatc agctcaatgt ctttgagtat taattttatg 1441 taagcattct atttaacatg aatataggac aaatcatggc tatatctata gaccttggat 1501 aaactggatt gaccaattat acactcacgg tgactttttt attggtggga aggggattgg 1561 ggtggggcag gctggcttaa tgtaatatga gcaaccaaag tgggacttct gtctccccgc 1621 tatattccca ttgctctgaa tggttgattg aagggtcagg gaactagatt ttatggcttt 1681 agttcactgt gattgtacat ttatacttgg cctatgtgct ggccgcacct gaacatagct 1741 ggtgcttatg ccgagttatt tgcgatgagt aaatatttag tttctttttc ttcatattta 1801 taatgttgat ctggcatcct caggctgcag ctttattagc ttataactta ctcatctcta 1861 tctttaccag caggctctgt attgttgata tttgcaactt gttttgcttt tccattggtg 1921 gaattgaaat aattagtttt taattacata agatgcctgt ttgctatttg gtggaagata 1981 gatgttcata ttgaagcagt cacatttgta ctgtagttca ataaaagaaa aatgaagtat 2041 tctgtagcct atatttttca tagagctcat gagcatttac tgtacttgct gggtcttgcc 2101 aagatcattt attccgctgc attgccaaag tgtcttcata ccaaattaaa ggtggtttta 2161 atatatgttt catggaagtt gtttataaaa ttcaaaggta tttcatttag gtgaaaagtc 2221 ttatttatta aagtggtttg aataaagtag atcaaaactt ccagagatct taatggctat 2281 ataggaagaa atatcactca ccataattta aataaagaat aaaaatactt gtattttgtg 2341 gtggcaaatg tttggtagaa ctgtaattag aaaaatacaa gtatatttgc gtgatggtta 2401 cactagaagc ccagacttta cgactacaca atatattcat gtatctaaac tgtacttgta 2461 ccccctaaat ttatttttaa aaaaggaaaa ataaaagtat catgaaaaaa cctatttttt 2521 tttccactgt ccttccacta ctcccataac aaacttatcc atggttggta aaattttaca 2581 tatttctatc cttgaaatga aggcttcttt taaattccaa agaagtcatg gaggcctgtg 2641 catttgaatt gtatatgcta gtgaggaaaa gatttagaca tttcaagagc agggttggcc 2701 aggcgcggtg gctcacacct gtaatcccag cactttggga ggccgaggag ggcggatcac 2761 gaggtcagga gatcgagacc atcctggcta acacagtgaa accccatctc tactaaaaaa 2821 aaaa

One example of a nucleic acid sequence for human RXRG is available as NCBI accession number NM_(—)006917 (gi: 58331205). This sequence is recited below for easy reference as SEQ ID NO:159.

   1 gtggcaagag tagcggtgac ggcggcggcg gcggcggcgg cagcattatg cgtgattact   61 gacaggcacc agctgctgcc gccacagccg tctcaaacgc actatgtgga ctctccgatc  121 tagaggcaga ttcctgacta atcccagagg gctggcccag cctgtgctcc ccgggctgct  181 aggaagcgat gaccactctt gttagcccaa gttgaagaaa gccgggctgt gcctgggagc  241 cgagagaggc ggtaatattt agaagctgca caggagagga acatgaactg acgagtaaac  301 atgtatggaa attattctca cttcatgaag tttcccgcag gctatggagg ctcccctggc  361 cacactggct ctacatccat gagcccatca gcagccttgt ccacagggaa gccaatggac  421 agccacccca gctacacaga taccccagtg agtgccccac ggactctgag tgcagtgggg  481 acccccctca atgccctggg ctctccatat cgagtcatca cctctgccat gggcccaccc  541 tcaggagcac ttgcagcgcc tccaggaatc aacttggttg ccccacccag ctctcagcta  601 aatgtggtca acagtgtcag cagttcagag gacatcaagc ccttaccagg gcttcccggg  661 attggaaaca tgaactaccc atccaccagc cccggatctc tggttaaaca catctgtgcc  721 atctgtggag acagatcctc aggaaagcac tacggggtat acagttgtga aggctgcaaa  781 gggttcttca agaggacgat aaggaaggac ctcatctaca cgtgtcggga taataaagac  841 tgcctcattg acaagcgtca gcgcaaccgc tgccagtact gtcgctatca gaagtgcctt  901 gtcatgggca tgaagaggga agctgtgcaa gaagaaagac agaggagccg agagcgagct  961 gagagtgagg cagaatgtgc taccagtggt catgaagaca tgcctgtgga gaggattcta 1021 gaagctgaac ttgctgttga accaaagaca gaatcctatg gtgacatgaa tatggagaac 1081 tcgacaaatg accctgttac caacatatgt catgctgctg acaagcagct tttcaccctc 1141 gttgaatggg ccaagcgtat tccccacttc tctgacctca ccttggagga ccaggtcatt 1201 ttgcttcggg cagggtggaa tgaattgctg attgcctctt tctcccaccg ctcagtttcc 1261 gtgcaggatg gcatccttct ggccacgggt ttacatgtcc accggagcag tgcccacagt 1321 gctggggtcg gctccatctt tgacagagtc ctaactgagc tggtttccaa aatgaaagac 1381 atgcagatgg acaagtcgga actgggatgc ctgcgagcca ttgtactctt taacccagat 1441 gccaagggcc tgtccaaccc ctctgaggtg gagactctgc gagagaaggt ttatgccacc 1501 cttgaggcct acaccaagca gaagtatccg gaacagccag gcaggtttgc caagctgctg 1561 ctgcgcctcc cagctctgcg ttccattggc ttgaaatgcc tggagcacct cttcttcttc 1621 aagctcatcg gggacacccc cattgacacc ttcctcatgg agatgttgga gaccccgctg 1681 cagatcacct gagccccacc agccacagcc tccccaccca ggatgacccc tgggcaggtg 1741 tgtgtggacc cccaccctgc actttcctcc acctcccacc ctgaccccct tcctgtcccc 1801 aaaatgtgat gcttataata aagaaaacct ttctacacat gaaaaaaaaa aaaaaa

One example of a nucleic acid sequence for human SDC4 is available as NCBI accession number NM_(—)002999 (gi: 38201674). This sequence is recited below for easy reference as SEQ ID NO:160.

   1 actcgccgca gcctgcgcgc cttctccagt ccgcggtgcc atggcccccg cccgtctgtt   61 cgcgctgctg ctgttcttcg taggcggagt cgccgagtcg atccgagaga ctgaggtcat  121 cgacccccag gacctcctag aaggccgata cttctccgga gccctaccag acgatgagga  181 tgtagtgggg cccgggcagg aatctgatga ctttgagctg tctggctctg gagatctgga  241 tgacttggaa gactccatga tcggccctga agttgtccat cccttggtgc ctctagataa  301 ccatatccct gagagggcag ggtctgggag ccaagtcccc accgaaccca agaaactaga  361 ggagaatgag gttatcccca agagaatctc acccgttgaa gagagtgagg atgtgtccaa  421 caaggtgtca atgtccagca ctgtgcaggg cagcaacatc tttgagagaa cggaggtcct  481 ggcagctctg attgtgggtg gcatcgtggg catcctcttt gccgtcttcc tgatcctact  541 gctcatgtac cgtatgaaga agaaggatga aggcagctat gacctgggca agaaacccat  601 ctacaagaaa gcccccacca atgagttcta cgcgtgaagc ttgcttgtgg gcactggctt  661 ggactttagc ggggagggaa gccaggggat tttgaagggt ggacattagg gtagggtgag  721 gtcaacctaa tactgacttg tcagtatctc cagctctgat tacctttgaa gtgttcagaa  781 gagacattgt cttctactgt tctgccaggt tcttcttgag ctttgggcct cagttgccct  841 ggcagaaaaa tggattcaac ttggcctttc tgaaggcaag actgggattg gatcacttct  901 taaacttcca gttaagaatc taggtccgcc ctcaagccca tactgaccat gcctcatcca  961 gagctcctct gaagccaggg ggctaacgga tgttgtgtgg agtcctggct ggaggtcctc 1021 ccccagtggc cttcctccct tcctttcaca gccggtctct ctgccaggaa atgggggaag 1081 gaactagaac cacctgcacc ttgagatgtt tctgtaaatg ggtacttgtg atcacactac 1141 gggaatctct gtggtatata cctggggcca ttctaggctc tttcaagtga cttttggaaa 1201 tcaacctttt ttatttgggg gggaggatgg ggaaaagagc tgagagttta tgctgaaatg 1261 gatttataga atatttgtaa atctattttt agtgtttgtt cgttttttta actgttcatt 1321 cctttgtgca gagtgtatat ctctgcctgg gcaagagtgt ggaggtgccg aggtgtcttc 1381 attctctcgc acatttccac agcacctgct aagtttgtat ttaatggttt ttgtttttgt 1441 ttttgtttgt ttcttgaaaa tgagagaaga gccggagaga tgatttttat taattttttt 1501 tttttttttt tttttttact atttatagct ttagataggg cctcccttcc cctcttcttt 1561 ctttgttctc tttcattaaa ccccttcccc agtttttttt ttatacttta aaccccgctc 1621 ctcatggcct tggccctttc tgaagctgct tcctcttata aaatagcttt tgccgaaaca 1681 tagttttttt ttagcagatc ccaaaatata atgaagggga tggtgggata tttgtgtctg 1741 tgttcttata atatattatt attcttcctt ggttctagaa aaatagataa atatattttt 1801 ttcaggaaat agtgtggtgt ttccagtttg atgttgctgg gtggttgagt gagtgaattt 1861 tcatgtggct gggtgggttt ttgccttttt ctcttgccct gttcctggtg ccttctgatg 1921 gggctggaat agttgaggtg gatggttcta ccctttctgc cttctgtttg ggacccagct 1981 ggtgttcttt ggtttgcttt cttcaggctc tagggctgtg ctatccaata cagtaaccac 2041 atgcggctgt ttaaagttaa gccaattaaa atcacataag attaaaaatt ccttcctcag 2101 ttgcactaac cacgtttcta gaggcgtcac tgtatgtagt tcatggctac tgtactgaca 2161 gcgagagcat gtccatctgt tggacagcac tattctagag aactaaactg gcttaacgag 2221 tcacagcctc agctgtgctg ggacgaccct tgtctccctg ggtagggggg ggggaatggg 2281 ggagggctga tgaggcccca gctggggcct gttgtctggg accctccctc tcctgagagg 2341 ggaggcctgg tggcttagcc tgggcaggtc gtgtctcctc ctgaccccag tggctgcggt 2401 gaggggaacc accctccctt gctgcaccag tggccattag ctcccgtcac cactgcaacc 2461 cagggtccca gctggctggg tcctcttctg cccccagtgc ccttcccctt gggctgtgtt 2521 ggagtgagca cctcctctgt aggcacctct cacactgttg tctgttactg attttttttg 2581 ataaaaagat aataaaacct ggtactttct aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

One example of a nucleic acid sequence for human SERPINA1 is available as NCBI accession number NM_(—)001127707 (gi: 189163541). This sequence is recited below for easy reference as SEQ ID NO:161.

   1 tgggcaggaa ctgggcactg tgcccagggc atgcactgcc tccacgcagc aaccctcaga   61 gtcctgagct gaaccaagaa ggaggagggg gtcgggcctc cgaggaaggc ctagccgctg  121 ctgctgccag gaattccagg ttggaggggc ggcaacctcc tgccagcctt caggccactc  181 tcctgtgcct gccagaagag acagagcttg aggagagctt gaggagagca ggaaagcctc  241 ccccgttgcc cctctggatc cactgcttaa atacggacga ggacagggcc ctgtctcctc  301 agcttcaggc accaccactg acctgggaca gtgaatcgac aatgccgtct tctgtctcgt  361 ggggcatcct cctgctggca ggcctgtgct gcctggtccc tgtctccctg gctgaggatc  421 cccagggaga tgctgcccag aagacagata catcccacca tgatcaggat cacccaacct  481 tcaacaagat cacccccaac ctggctgagt tcgccttcag cctataccgc cagctggcac  541 accagtccaa cagcaccaat atcttcttct ccccagtgag catcgctaca gcctttgcaa  601 tgctctccct ggggaccaag gctgacactc acgatgaaat cctggagggc ctgaatttca  661 acctcacgga gattccggag gctcagatcc atgaaggctt ccaggaactc ctccgtaccc  721 tcaaccagcc agacagccag ctccagctga ccaccggcaa tggcctgttc ctcagcgagg  781 gcctgaagct agtggataag tttttggagg atgttaaaaa gttgtaccac tcagaagcct  841 tcactgtcaa cttcggggac accgaagagg ccaagaaaca gatcaacgat tacgtggaga  901 agggtactca agggaaaatt gtggatttgg tcaaggagct tgacagagac acagtttttg  961 ctctggtgaa ttacatcttc tttaaaggca aatgggagag accctttgaa gtcaaggaca 1021 ccgaggaaga ggacttccac gtggaccagg tgaccaccgt gaaggtgcct atgatgaagc 1081 gtttaggcat gtttaacatc cagcactgta agaagctgtc cagctgggtg ctgctgatga 1141 aatacctggg caatgccacc gccatcttct tcctgcctga tgaggggaaa ctacagcacc 1201 tggaaaatga actcacccac gatatcatca ccaagttcct ggaaaatgaa gacagaaggt 1261 ctgccagctt acatttaccc aaactgtcca ttactggaac ctatgatctg aagagcgtcc 1321 tgggtcaact gggcatcact aaggtcttca gcaatggggc tgacctctcc ggggtcacag 1381 aggaggcacc cctgaagctc tccaaggccg tgcataaggc tgtgctgacc atcgacgaga 1441 aagggactga agctgctggg gccatgtttt tagaggccat acccatgtct atcccccccg 1501 aggtcaagtt caacaaaccc tttgtcttct taatgattga acaaaatacc aagtctcccc 1561 tcttcatggg aaaagtggtg aatcccaccc aaaaataact gcctctcgct cctcaacccc 1621 tcccctccat ccctggcccc ctccctggat gacattaaag aagggttgag ctggtccctg 1681 cctgcatgtg actgtaaatc cctcccatgt tttctctgag tctccctttg cctgctgagg 1741 ctgtatgtgg gctccaggta acagtgctgt cttcgggccc cctgaactgt gttcatggag 1801 catctggctg ggtaggcaca tgctgggctt gaatccaggg gggactgaat cctcagctta 1861 cggacctggg cccatctgtt tctggagggc tccagtcttc cttgtcctgt cttggagtcc 1921 ccaagaagga atcacagggg aggaaccaga taccagccat gaccccaggc tccaccaagc 1981 atcttcatgt ccccctgctc atcccccact cccccccacc cagagttgct catcctgcca 2041 gggctggctg tgcccacccc aaggctgccc tcctgggggc cccagaactg cctgatcgtg 2101 ccgtggccca gttttgtggc atctgcagca acacaagaga gaggacaatg tcctcctctt 2161 gacccgctgt cacctaacca gactcgggcc ctgcacctct caggcacttc tggaaaatga 2221 ctgaggcaga ttcttcctga agcccattct ccatggggca acaaggacac ctattctgtc 2281 cttgtccttc catcgctgcc ccagaaagcc tcacatatct ccgtttagaa tcaggtccct 2341 tctccccaga tgaagaggag ggtctctgct ttgttttctc tatctcctcc tcagacttga 2401 ccaggcccag caggccccag aagaccatta ccctatatcc cttctcctcc ctagtcacat 2461 ggccataggc ctgctgatgg ctcaggaagg ccattgcaag gactcctcag ctatgggaga 2521 ggaagcacat cacccattga cccccgcaac ccctcccttt cctcctctga gtcccgactg 2581 gggccacatg cagcctgact tctttgtgcc tgttgctgtc cctgcagtct tcagagggcc 2641 accgcagctc cagtgccacg gcaggaggct gttcctgaat agcccctgtg gtaagggcca 2701 ggagagtcct tccatcctcc aaggccctgc taaaggacac agcagccagg aagtcccctg 2761 ggcccctagc tgaaggacag cctgctccct ccgtctctac caggaatggc cttgtcctat 2821 ggaaggcact gccccatccc aaactaatct aggaatcact gtctaaccac tcactgtcat 2881 gaatgtgtac ttaaaggatg aggttgagtc ataccaaata gtgatttcga tagttcaaaa 2941 tggtgaaatt agcaattcta catgattcag tctaatcaat ggataccgac tgtttcccac 3001 acaagtctcc tgttctctta agcttactca ctgacagcct ttcactctcc acaaatacat 3061 taaagatatg gccatcacca agccccctag gatgacacca gacctgagag tctgaagacc 3121 tggatccaag ttctgacttt tccccctgac agctgtgtga ccttcgtgaa gtcgccaaac 3181 ctctctgagc cccagtcatt gctagtaaga cctgcctttg agttggtatg atgttcaagt 3241 tagataacaa aatgtttata cccattagaa cagagaataa atagaactac atttcttgca

One example of a nucleic acid sequence for human SLC25A15 is available as NCBI accession number NM_(—)014252 (gi: 237649033). This sequence is recited below for easy reference as SEQ ID NO:162.

   1 tgggggcggt ggcagggccg gtgggcggtg gcggctcccg gtctcggctc gggcacggcc   61 ctgggcaggc cgcccgccag ccgcaggggc gctcctgagc ttcgcggggc cgcagtccgg  121 gatgcctgcg cgaagggagg ggcgaagggc cggccgttgc cgacgtgggt gttaagtggc  181 cgccccagcc ggcgacccgg agccgagagc gggcggcgga gcctgagctg gacgcggcca  241 cgccggcgcg gcgggatatg tggtgcctgt cataagctcc agagagctgc cttccacaag  301 accagcagaa gagtgggcaa acatgaaatc caatcctgct atccaggctg ccattgacct  361 cacagcgggg gctgcaggag gtacagcatg tgtactgacc gggcagccct ttgacacaat  421 gaaagtgaag atgcagacgt tccctgacct gtaccggggc ctcaccgact gctgcctgaa  481 gacttactcc caggtgggct tccgtggctt ctacaagggt accagtccag cactaatcgc  541 caacatcgct gagaactcag tcctcttcat gtgctacggc ttctgccagc aggtggtgcg  601 gaaagtggct ggattggaca agcaggcaaa gctgagtgat ctgcagaatg cagccgccgg  661 ttccttcgcc tctgcctttg ctgcactggt gctctgcccc acggagctcg tgaagtgccg  721 gctgcagacc atgtatgaga tggagacatc agggaagata gccaagagcc agaatacagt  781 gtggtctgtc atcaaaagta ttcttaggaa agatggcccc ttggggttct accatggact  841 ctcaagcact ttacttcgag aagtaccagg ctatttcttc ttcttcggtg gctatgaact  901 gagccggtcc ttttttgcat cagggagatc aaaagatgaa ttaggccctg tacctttgat  961 gttaagtggt ggagttggtg ggatttgcct ctggcttgcg gtatacccag tggattgtat 1021 caaatccaga attcaagttc tttccatgtc tggaaaacag gcaggattta tcagaacctt 1081 tataaatgtt gtgaaaaatg aaggaataac ggccttatat tctggactga aacctactat 1141 gattcgagca ttccctgcca atggagcact ctttttggcc tacgaatata gcaggaagtt 1201 gatgatgaac cagttggaag catactgaag tgtcttggtg ggcctgagcc aagcacaggt 1261 gtttgaggac tacagttcat ctcagggttt cttggagtac aagaccagtg tgaagttatt 1321 ctgatttctt gggaattttg ctttttgtct tcccttctac cctacatctt aaactttatg 1381 gaagaacctc tattttgcat catatcattt ctgtccataa ttgtactgaa atagaaaagt 1441 gaccgctctt gctcttggta aaatatagag tggtcagtag ccttatgcac ctaattcaaa 1501 aggtggaata tagttctgtc agggctttta cgtaaacctc cacttgtaca tgcaatttgg 1561 acagttatgt gttgagggaa atacagtttg gtaccttgtt tatttcaaat atcagaaaaa 1621 cccagaggtg atcatttctc atgaagatgc ttataaatgg ttgcttaacc cattctagat 1681 gtagggtctg cttaatgtgt gtacttttct aagtggttga ttatttttta tttttttgat 1741 acagagtctc actctgtcac ccagactgga gtgcagtggc acgatctcgg ctcactgcaa 1801 cctccgcctc ctgggttcaa gcgattctct cacctcagcc tcctgagtag ctgggattac 1861 aggtacgcgc caccatgtcc agctaatttt ttttggtatt ttttgtagag acgaggtttc 1921 accatgttgt ccaggttggt ctcgaactcc tgacctcaag tgatccgccc acctcggcct 1981 cccaaagtgc tgggattact ggtgtgagcc accatgccca gccagtggtt gaatttttta 2041 aaaagtgttc atggggtgct tgaaaactaa aatatccttc tagatttgta agacagtata 2101 cctgcatact ggtgtggctt ccacacttga gtaaaagctt cagagtaggt atcctagatt 2161 tccccaagat gctctactct taaaatagtg ccattcattt tctaggtggg atcatattcc 2221 acgctgacta tattgctagg ggtggcccag agggtcaggc ctttgggaaa tagcatggcc 2281 tttaccagct tcccttctct cccaaagaac ttcccttctt gggctttaga ttgaggaagg 2341 ggctgagtgg taggcggtgc tgctgtgctc tgatgaagac ccatgtggct agcaacagcg 2401 cttacctttt gtctctgggt cctggcctgg ggccatcaat ccactttggg ccactcactg 2461 tctgctctgc ctccaccaat cagaaaccct tccaaggaac agtgagagcc aaagccaaga 2521 gaagccttct tccctgtttg gtgattgtgt gacagtgggt gaacctctct cagagagaac 2581 tagaaagaac tcagtgcttg tactccacag tgagtaatgt caggtctgac ccatcctgaa 2641 gcctgtcttg ccatgctttt acagtgttgg aggcttctac atttggtact tgcagtcagt 2701 aagtcttaat gatgactgta tatgtgatat gagtttataa agcaatggaa cataagaaaa 2761 gcaattgtag gccaggcgca gtggctcacg cctataatcc cagcactttg ggaggctgag 2821 gcgggcgggt cacaaggtca ggagttcgag aacagcctga ccaacatggt gaaaccccat 2881 ctctactaaa aatacaaaaa ttagctgggc gtggtggcac gtgcctgtaa tcccagctac 2941 tcaggaggct gaggcaggag aatcgcttga acccgggagg cagaggttgc agtgaactga 3001 gattgtgcca ctgcactcca gactgggtga cacagcgaga cttcatctca aaaaaaaaaa 3061 gaaaagaaaa gcaattgtac ttcactatgc catatgtatg tattcactga ccaaaaattc 3121 actgaccaac caaccaaact ccacacttca tctgatcccc catagacttg gggatggaca 3181 gctgttcttt ggccatatgg tataagagga tcattcttgt cactacttaa gttagcctca 3241 tcattttgtg ctgctccaac accagcaggg tatctcccaa taaagtgttc ctaagcagcc 3301 tgtatactga gtgcaagcag gctatcaatt ttaataatag tccataccat gtatgtgttt 3361 ctgtcagcag aatgtacatg ttgtacaaaa cctccaggtt ccttaagctt tttgctgtcc 3421 atgaatcctc tgtggcaact gtaatcacag agccagaagc cagagggcca gggatatgag 3481 aggctgacaa acatcagggg acatctgggg aggagatccc tgtcatgtct cttgtgccat 3541 ggagctatta tggctggtct tccatttgct ttttctttaa gtgaaaacca tttttctact 3601 ttgcttttct ctccatactt aaatggtcag tagctactga gtggtgcttt atctgaatag 3661 gcctggatcg aagtaaaata gaaatgggac tggctttcca caggaagtaa actgcttcag 3721 agcccacagt cccctgctca gtgtccggaa agaagtcagt catccctgtt ggcagtaaat 3781 cttcccacag gccgtccatt agagatttaa ctagatatgt tcaatagaaa gagtctgagg 3841 caagtggaaa tgaggaacgg aaacttaggt tgggagaata tttttttttt attcattctg 3901 tttgcttaat tcagagtaca gtttgtgcta tttcatatct gtactccagg cagaaatata 3961 acttgaaaat actgtgtcta aagaaatttc agtgttctat cattaaatta tttacttaat 4021 aaaaaaaaaa aaaaaaaa

One example of a nucleic acid sequence for human SLC4A4 is available as NCBI accession number NM_(—)001098484 (gi: 197927157). This sequence is recited below for easy reference as SEQ ID NO:163.

   1 gcggcggcgg ccgcggtggc agcgaaggcg gcggcggcgg cggcagtggc agtggccgct   61 gcagccccac actccgccgc caaactggag gagcgacgga agccagaccc caggaggatg  121 gaggatgaag ctgtcctgga cagaggggct tccttcctca agcatgtgtg tgatgaagaa  181 gaagtagaag gccaccatac catttacatc ggagtccatg tgccgaagag ttacaggaga  241 aggagacgtc acaagagaaa gacagggcac aaagaaaaga aggaaaagga gagaatctct  301 gagaactact ctgacaaatc agatattgaa aatgctgatg aatccagcag cagcatccta  361 aaacctctca tctctcctgc tgcagaacgc atccgattca tcttgggaga ggaggatgac  421 agcccagctc cccctcagct cttcacggaa ctggatgagc tgctggccgt ggatgggcag  481 gagatggagt ggaaggaaac agccaggtgg atcaagtttg aagaaaaagt ggaacagggt  541 ggggaaagat ggagcaagcc ccatgtggcc acattgtccc ttcatagttt atttgagctg  601 aggacatgta tggagaaagg atccatcatg cttgatcggg aggcttcttc tctcccacag  661 ttggtggaga tgattgttga ccatcagatt gagacaggcc tattgaaacc tgaacttaag  721 gataaggtga cctatacttt gctccggaag caccggcatc aaaccaagaa atccaacctt  781 cggtccctgg ctgacattgg gaagacagtc tccagtgcaa gtaggatgtt taccaaccct  841 gataatggta gcccagccat gacccatagg aatctgactt cctccagtct gaatgacatt  901 tctgataaac cggagaagga ccagctgaag aataagttca tgaaaaaatt gccacgtgat  961 gcagaagctt ccaacgtgct tgttggggag gttgactttt tggatactcc tttcattgcc 1021 tttgttaggc tacagcaggc tgtcatgctg ggtgccctga ctgaagttcc tgtgcccaca 1081 aggttcttgt tcattctctt aggtcctaag gggaaagcca agtcctacca cgagattggc 1141 agagccattg ccaccctgat gtctgatgag gtgttccatg acattgctta taaagcaaaa 1201 gacaggcacg acctgattgc tggtattgat gagttcctag atgaagtcat cgtccttcca 1261 cctggggaat gggatccagc aattaggata gagcctccta agagtcttcc atcctctgac 1321 aaaagaaaga atatgtactc aggtggagag aatgttcaga tgaatgggga tacgccccat 1381 gatggaggtc acggaggagg aggacatggg gattgtgaag aattgcagcg aactggacgg 1441 ttctgtggtg gactaattaa agacataaag aggaaagcgc cattttttgc cagtgatttt 1501 tatgatgctt taaatattca agctctttcg gcaattctct tcatttatct ggcaactgta 1561 actaatgcta tcacttttgg aggactgctt ggggatgcca ctgacaacat gcagggcgtg 1621 ttggagagtt tcctgggcac tgctgtctct ggagccatct tttgcctttt tgctggtcaa 1681 ccactcacta ttctgagcag caccggacct gtcctagttt ttgagaggct tctatttaat 1741 ttcagcaagg acaataattt tgactatttg gagtttcgcc tttggattgg cctgtggtcc 1801 gccttcctat gtctcatttt ggtagccact gatgccagct tcttggttca atacttcaca 1861 cgtttcacgg aggagggctt ttcctctctg attagcttca tctttatcta tgatgctttc 1921 aagaagatga tcaagcttgc agattactac cccatcaact ccaacttcaa agtgggctac 1981 aacactctct tttcctgtac ctgtgtgcca cctgacccag ctaatatctc aatatctaat 2041 gacaccacac tggccccaga gtatttgcca actatgtctt ctactgacat gtaccataat 2101 actacctttg actgggcatt tttgtcgaag aaggagtgtt caaaatacgg aggaaacctc 2161 gtcgggaaca actgtaattt tgttcctgat atcacactca tgtcttttat cctcttcttg 2221 ggaacctaca cctcttccat ggctctgaaa aaattcaaaa ctagtcctta ttttccaacc 2281 acagcaagaa aactgatcag tgattttgcc attatcttgt ccattctcat cttttgtgta 2341 atagatgccc tagtaggcgt ggacacccca aaactaattg tgccaagtga gttcaagcca 2401 acaagtccaa accgaggttg gttcgttcca ccgtttggag aaaacccctg gtgggtgtgc 2461 cttgctgctg ctatcccggc tttgttggtc actatactga ttttcatgga ccaacaaatt 2521 acagctgtga ttgtaaacag gaaagaacat aaactcaaga aaggagcagg gtatcacttg 2581 gatctctttt gggtggccat cctcatggtt atatgctccc tcatggctct tccgtggtat 2641 gtagctgcta cggtcatctc cattgctcac atcgacagtt tgaagatgga gacagagact 2701 tctgcacctg gagaacaacc aaagtttcta ggagtgaggg aacaaagagt cactggaacc 2761 cttgtgttta ttctgactgg tctgtcagtc tttatggctc ccatcttgaa gtttataccc 2821 atgcctgtac tctatggtgt gttcctgtat atgggagtag catcccttaa tggtgtgcag 2881 ttcatggatc gtctgaagct gcttctgatg cctctgaagc atcagcctga cttcatctac 2941 ctgcgtcatg ttcctctgcg cagagtccac ctgttcactt tcctgcaggt gttgtgtctg 3001 gccctgcttt ggatcctcaa gtcaacggtg gctgctatca tttttccagt aatgatcttg 3061 gcacttgtag ctgtcagaaa aggcatggac tacctcttct cccagcatga cctcagcttc 3121 ctggatgatg tcattccaga aaaggacaag aaaaagaagg aggatgagaa gaaaaagaaa 3181 aagaagaagg gaagtctgga cagtgacaat gatgattctg actgcccata ctcagaaaaa 3241 gttccaagta ttaaaattcc aatggacatc atggaacagc aacctttcct aagcgatagc 3301 aaaccttctg acagagaaag atcaccaaca ttccttgaac gccacacatc atgctgataa 3361 aattcctttc cttcagtcac tcggtatgcc aagtcctcct agaactccag taaaagttgt 3421 gcctcaaatt agaatagaac ttgaacctga agacaatgat tatttctgga ggagcaaggg 3481 aacagaaact acattgtaac ctgtttgtct ttcttaaaac tgacatttgt tgttaatgtc 3541 atttgttttt gtttggctgt ttgtttattt tttaactttt atttcgtctc agtttttggt 3601 cacaggccaa ataatacagc gctctctctg cttctctctt gcatagatac aatcaagaca 3661 atagtgcacc gttccttaaa aacagcatct gaggaatccc ccttttgttc ttaaactttc 3721 agatgtgtcc tttgataacc aaattctgtc actcaagaca cagacacgca cagaccctgt 3781 cctttgcctc tattaagcag aggatggaag tattaaggat tttgtaacac cttttatgaa 3841 aatgttgaag gaacttaaaa ctttagcttt ggagctgtgc ttactggctt gtctttgtct 3901 ggtagaacaa accttgacct ccagacagag tcccttctca cttatagagc tctccaggac 3961 tggaaaaagt gctgctattt taacttgctc ttgcttgtaa atcctaatct tagagttatc 4021 aaaagaagaa aaaactgaag gtactttact ccctatagag aaaccattgc catcattgta 4081 gcaagtgctg gaatgtccct tttttcctat gcaacttttt ttaacccttt aatgaactta 4141 tctgttgagt acattgaaga atatttttct tcctagattt tgttgtttaa attatggggc 4201 ctaacctgcc acttattttt tgtcaatttt taaaactttt ttttaattac tgtaaagaaa 4261 atgaattttt tcctgcagca ggaaacatag ttttgagtag ttctacctct tatttgtagc 4321 tgccaggctt tctgtaaaaa ttgtattgta tataatgtga tttttacaca tacatacaca 4381 cacaaataca caatctctag ggtaagccag aaggcaagat cagattaaaa acaccatgtt 4441 tctaagcatc catttttccc tttctttaaa agaaacttaa ctgttctatg aaggagattg 4501 agggagaaga gacaaactcc tatgtcatga gaataaccga tgttctgata atagtagcat 4561 ctaggtacag atgctggttg tattaccacg tcaatgtcct atgcagtatt gttagacatt 4621 ttctcatttt gaaatatttg tgtgtttgtg tatgtgctct gtgccatggc tggtgtatat 4681 atgtgcaatg ttagaaggca aaagagtgat ggtaggcaga gggcaaagtc attgaatctc 4741 ttatgccagt tttcataaaa cccaaaccac atatgaaaaa atccattaag ggtccaagaa 4801 gtctgtccat atgaaaatga gggtaaatat agtttatttc ccaggtatca gtcattataa 4861 ttgatataat agctctaaca tgcaatataa aattcatagg agtattaata gcccatttac 4921 acatctataa aatgtaatgg gattgcagag ctgcagagta cagtgtaaca gtactctcat 4981 gcaatttttt tcaggatgca aaggcaatta ttctttgtaa gcgggacatt tagaatatat 5041 ttgtgtacat attatatgta tgtatatttc aaagtaccac actgaaaatt agacatttat 5101 taaccaaatt taacgtggta tttaaaggta atatttttaa tatgatacat tacatattgt 5161 gaatgtatac taaaaaaaca ttttaaatgt taaaattata atttcagatt catataacca 5221 caactgtgat atatcctaac tataaccagt tgttgagggg tatactagaa gcagaatgaa 5281 accacatttt ttggtttgat aatatgcact tattgactcc cactcattgt tatgttaatt 5341 aagttattat tctgtctcct tgtaattttg attacaaaaa ttttattatc ctgagttagc 5401 tgttactttt acagtacctg atactcctaa aacttttaac ttatacaaat tagtcaataa 5461 tgaccccaat tttttcatta aaataatagt ggtgaattat atgttattgt gttaaaacct 5521 cacttgccaa attctggctt cacatttgta tttagggcta tccttaaaat gatgagtcta 5581 tattatctag ctttctatta ccctaatata aactggtata agaagacttt ccttttttct 5641 ttatgcatgg aagcatcaat aaattgttta aaaaccatgt atagtaaatt cagcttaacc 5701 cgtgatcttc ttaagttaaa ggtacttttg ttttataaaa gctctagata aaactttctt 5761 ttctgatcat gaatcaagta tctgtggttt catgcccctc tctatacctt tcaaagaact 5821 cctgaagcaa cttaactcat catttcagcc tctgagtaga ggtaaaacct atgtgtactt 5881 ctgtttatga tccatattga tatttatgac atgaacacag aatagtacct tacatttgct 5941 aaacagacag ttaatatcaa atcctttcaa tattctggga acccagggaa gtttttaaaa 6001 atgtcattac tttcaaagga acagaagtag ttaaccaaac taacaagcaa aacctgaggt 6061 ttacctagtg acaccaaatt atcggtattt taactgaatt tacccattga ctaagaatga 6121 accagatttg gtggtggttt tgtttctatg caaactggac acaaattaca acagtaaatt 6181 tttttataag tgcttctccc ttctccatga tgtgacttcc ggagataaag gattcaaaag 6241 ataaagacaa agtacgctca gagttgttaa ccagaaagtc ctggctgtgg ttgcagaaac 6301 actgttggaa gaaaagagat gactaagtca agtgtctgcc ttatcaaaag agcaaaaatg 6361 cctctggttt tgtgtttggg agaaaaatat cttggacgca ctgttttcct tgataaaagt 6421 catcttctct actgtgtgaa atgaatactt ggaattctaa ttgttttgtg tgccaggggc 6481 agtaatgtcc ctgcctcttc tcccaatcaa ggttgaggag tggggctggg gagaggactt 6541 aactgactta agaagtagga aaacaaaaac ctctctcctc agccttccac ctccaagaga 6601 ggaggaaaaa cagttgtctg ctgtctgtaa ttcagtttgc gtgtatttta tgctcatgca 6661 ccaacccata cagagtaaat cttttatcaa ctatatactg gtgtttaata gagaatgatt 6721 gtcttccgag ttttttggtt ccttttttaa ctgtgttaaa gtacttgaaa tgtattgact 6781 gctgactata ttttaaaaac aaaatgaaat aatttgagtt gtattacaga ggttgacatt 6841 gttcagggat gggacaaagc cttcttcaat ccttttcata ctacttaatg attttggtgc 6901 aggaacctga gattttctga tttatatttc atgatatttc acatttgctc ttcacagcat 6961 gagcatgaag cccagtggca ccaaatggct gggtacaatc aagtgatatt ttgtagcacc 7021 tcactatctg aaaggccatg agttttcaga tgatttcatt gagcttcatt gcagcctgaa 7081 attttaaaaa agttgtgtaa tacgccaacc agtcaagttg tgttttggcc agagatttag 7141 atatgtccaa tttcctggct catttcattg tgctctatgg gtacgtataa aaagcaagaa 7201 ttctgtttcc taggcaaaca ttgcaactca gggctaaagt catccagtga aacttttaga 7261 gccagaagta actttgtccc agtcctacaa tgtgaaaaga gtgaatagtt gcctcttttt 7321 agccattttc atggctggta catattcgta cgcattactt ttcagaatca atacgcactt 7381 tcagatattc ttatttttat tctcttaagt ctttattaac tttggagaga gaaatgatgc 7441 atctttttat tttaaatgaa gtagatcaac atggtggaac aaaatgataa agaacagaaa 7501 acatttcaat atattactaa taactttttc caatataaat cctaaaattc ctataacata 7561 gtattttaca gttttatgaa gctttctatt gtgactttta tggaattaag agatgaagaa 7621 gatgagatat tttagcattt atatttttca aaattatatg tatacttaaa aataaagtaa 7681 ctttatgcat tta

One example of a nucleic acid sequence for human SLIT1 is available as NCBI accession number NM_(—)003061 (gi: 188528674). This sequence is recited below for easy reference as SEQ ID NO:164.

   1 gggagaggga gacgcaggcg gcgaaacggc agaggagccg agccccctcc gcccaaggcg   61 ccctccctcc gtccgcgcac aggcgccgtc gcttggagga gcaaggtgcc tcccagcccg  121 caggggcgcc gcgcgcaagc ccgcgggctc ttcggtggct ctgccccggg actgcacctg  181 gaggcggccc cggacgggga tggtcagcgg ctgctgccgt ctggctcgcg agcgggacgc  241 tgtgagggca ccatggcgct gactcccggg tgggggtcct cggcggggcc ggtccggccg  301 gagctctggc tgctgctgtg ggcagccgcg tggcgcctgg gtgcctcggc gtgccccgcc  361 ctctgcacct gcaccggaac cacggtggac tgccacggca cggggctgca ggccattccc  421 aagaatatac ctcggaacac cgagcgcctg gaactcaatg gcaacaacat cactcggatc  481 cataagaatg actttgcggg gctcaagcag ctgcgggtgc tgcagctgat ggagaaccag  541 attggagcag tggaacgtgg tgcttttgat gacatgaagg agctggagcg gctgcgactg  601 aaccgaaacc agctgcacat gttaccggaa ctgctgttcc agaacaacca ggctttgtca  661 agactggact tgagtgagaa cgccatccag gccatcccca ggaaagcttt tcggggagct  721 acggacctta aaaatttaca gctggacaag aaccagatca gctgcattga ggaaggggcc  781 ttccgtgctc tgcgggggct ggaggtgctg accctgaaca acaacaatat caccaccatc  841 cccgtgtcca gcttcaacca tatgcccaag ctacggacct tccgcctgca ctccaaccac  901 ctgttttgcg actgccacct ggcctggctc tcgcagtggc tgaggcagcg gccaaccatc  961 gggctcttca cccagtgctc gggcccagcc agcctgcgtg gcctcaatgt ggcagaggtc 1021 cagaagagtg agttcagctg ctcaggccag ggagaagcgg ggcgcgtgcc cacctgcacc 1081 ctgtcctccg gctcctgccc ggccatgtgc acctgcagca atggcatcgt ggactgtcgt 1141 ggaaaaggcc tcactgccat cccggccaac ctgcccgaga ccatgacgga gatacgcctg 1201 gagctgaacg gcatcaagtc catccctcct ggagccttct caccctacag aaagctacgg 1261 aggatagacc tgagcaacaa tcagatcgct gagattgcac ccgacgcctt ccagggcctc 1321 cgctccctga actcgctggt cctctatgga aacaagatca cagacctccc ccgtggtgtg 1381 tttggaggcc tatacaccct acagctcctg ctcctgaatg ccaacaagat caactgcatc 1441 cggcccgatg ccttccagga cctgcagaac ctctcactgc tctccctgta tgacaacaag 1501 atccagagcc tcgccaaggg cactttcacc tccctgcggg ccatccagac tctgcacctg 1561 gcgcagaacc ctttcatttg cgactgtaac ctcaagtggc tggcagactt cctgcgcacc 1621 aatcccatcg agacgagtgg tgcccgctgt gccagtcccc ggcgcctcgc caacaagcgc 1681 atcgggcaga tcaagagcaa gaagttccgg tgctcagcca aagagcagta cttcattcca 1741 ggcacggagg attaccagct gaacagcgag tgcaacagcg acgtggtctg tccccacaag 1801 tgccgctgtg aggccaacgt ggtggagtgc tccagcctga agctcaccaa gatccctgag 1861 cgcatccccc agtccacggc agaactgcga ttgaataaca atgagatttc catcctggag 1921 gccactggga tgtttaaaaa acttacacat ctgaagaaaa tcaatctgag caacaacaag 1981 gtgtcagaaa ttgaagatgg ggccttcgag ggcgcagcct ctgtgagcga gctgcaccta 2041 actgccaacc agctggagtc catccggagc ggcatgttcc ggggtctgga tggcttgagg 2101 accctaatgc tgcggaacaa ccgcatcagc tgcatccaca acgacagctt cacgggcctg 2161 cgcaacgtcc ggctcctctc gctctacgac aaccagatca ccaccgtatc cccaggagcc 2221 ttcgacaccc tccagtccct ctccacactg aatctcctgg ccaacccttt caactgcaac 2281 tgccagctgg cctggctagg aggctggcta cggaagcgca agatcgtgac ggggaacccg 2341 cgatgccaga accctgactt tttgcggcag attcccctgc aggacgtggc cttccctgac 2401 ttcaggtgtg aggaaggcca ggaggagggg ggctgcctgc cccgcccaca gtgcccacag 2461 gagtgcgcct gcctggacac cgtggtccga tgcagcaaca agcacctgcg ggccctgccc 2521 aagggcattc ccaagaatgt cacagaactc tatttggacg ggaaccagtt cacgctggtt 2581 ccgggacagc tgtctacctt caagtacctg cagctcgtgg acctgagcaa caacaagatc 2641 agttccttaa gcaattcctc cttcaccaac atgagccagc tgaccactct gatcctcagc 2701 tacaatgccc tgcagtgcat cccgcctttg gccttccagg gactccgctc cctgcgcctg 2761 ctgtctctcc acggcaatga catctccacc ctccaagagg gcatctttgc agacgtgacc 2821 tccctgtctc acctggccat tggtgccaac cccctatact gtgactgcca cctccgctgg 2881 ctgtccagct gggtgaagac tggctacaag gaaccgggca ttgctcgttg tgctgggccc 2941 caggacatgg agggcaagct gctcctcacc acgcctgcca agaagtttga atgccaaggt 3001 cctccaacgc tggctgtcca ggccaagtgt gatctctgct tgtccagtcc gtgccagaac 3061 cagggcacct gccacaacga cccccttgag gtgtacaggt gcgcctgccc cagcggctat 3121 aagggtcgag actgtgaggt gtccctggac agctgttcca gtggcccctg tgaaaatggg 3181 ggcacctgcc atgcacagga gggcgaggat gccccgttca cgtgctcctg tcccaccggc 3241 tttgaaggac caacctgtgg ggtgaacaca gatgactgtg tggatcatgc ctgtgccaat 3301 gggggcgtct gtgtggatgg tgtgggcaac tacacctgcc agtgccccct gcagtatgag 3361 ggaaaggcct gtgagcagct ggtggacttg tgctctccgg atctgaaccc atgtcaacac 3421 gaggcccagt gtgtgggcac cccggatggg cccaggtgtg agtgcatgcc aggttatgca 3481 ggtgacaact gcagtgagaa ccaggatgac tgcagggacc accgctgcca gaatggggcc 3541 cagtgtatgg atgaagtcaa cagctactcc tgcctctgtg ctgagggcta cagtggacag 3601 ctctgtgaga tccctcccca tctgcctgcc cccaagagcc cctgtgaggg gactgagtgc 3661 cagaatgggg ccaactgtgt ggaccagggc aacaggcctg tgtgccagtg cctcccaggc 3721 ttcggtggcc ctgagtgtga gaagttgctc agtgtcaact ttgtggatcg ggacacttac 3781 ctgcagttca ctgacctgca aaactggcca cgggccaaca tcacgttgca ggtctccacg 3841 gcagaggaca atgggatcct tctgtacaac ggggacaacg accacattgc agttgagctg 3901 taccagggcc atgtgcgtgt cagctacgac ccaggcagct accccagctc tgccatctac 3961 agtgctgaga cgatcaacga tgggcaattc cacaccgttg agctggttgc ctttgaccag 4021 atggtgaatc tctccattga tggcgggagc cccatgacca tggacaactt tggcaaacat 4081 tacacgctca acagcgaggc gccactctat gtgggaggga tgcccgtgga tgtcaactca 4141 gctgccttcc gcctgtggca gatcctcaac ggcaccggct tccacggttg catccgaaac 4201 ctgtacatca acaacgagct gcaggacttc accaagacgc agatgaagcc aggcgtggtg 4261 ccaggctgcg aaccctgccg caagctctac tgcctgcatg gcatctgcca gcccaatgcc 4321 accccagggc ccatgtgcca ctgcgaggct ggctgggtgg gcctgcactg tgaccagccc 4381 gctgacggcc cctgccatgg ccacaagtgt gtccatgggc aatgcgtgcc cctcgacgct 4441 ctttcctaca gctgccagtg ccaggatggg tactcggggg cactgtgcaa ccaggccggg 4501 gccctggcag agccctgcag aggcctgcag tgcctgcatg gccactgcca ggcctcaggc 4561 accaaggggg cacactgtgt gtgtgacccc ggcttttcgg gcgagctgtg tgagcaagag 4621 tccgagtgcc ggggggaccc tgtccgggac tttcaccagg tccagagggg ctatgccatc 4681 tgccagacca cgcgccccct gtcatgggtg gagtgccggg gctcgtgccc aggccagggc 4741 tgctgccagg gccttcggct gaagcggagg aagttcacct ttgagtgcag cgatgggacc 4801 tcttttgccg aggaggtgga aaagcccacc aagtgtggct gtgccctctg cgcatagcgc 4861 tgggcgtgga caggccggtg agggcgggca aggggcccca gccgctgcag cagcggagac 4921 agtcgccagc agctgggctg gggtggaggt catcacagga cggctcctgg gcagctgggc 4981 cctcctgggt ggggtggtgc cagagcagcc ttttaaaagc aaattgcgcc atagctgggg 5041 gcagcggggg tgggcgaggc ctgagctgcg ggctgccctc tccggaagtg ccttgcacaa 5101 ataggcgctt aataaatatt tgttgagtga atgtgtgcgt gaggtcaggc caagaagtgc 5161 agaacgatga cacccctcct tacctgctat ctgaatctgg agaagaaaaa tgacagcctt 5221 ccaaaccaac ccttcccttt ggcctgtggc ccaggctggc ttggaactgg gtctgtggcc 5281 ccagaagcct cttacccctc tgcgggcaac catgaagtac tgtcagcctc cccgggaagc 5341 cagcctggtt cattctgctg ctacagaatc tgctggtggt aggccaggct ctggagcggg 5401 ggtgccgcct cctgctggcc agggagggtc ggacccttgc cccctgggct gactggcagc 5461 tctgcagcca cggcttggga acgaggctgt gggtggaggt ggttcttagg accaggcctc 5521 tgaatcctaa agttctagca tgactactgt agctgcgagg gcttatgtgg aggaaacagt 5581 cacaggggct gctcagggtg gcagacccca ctaaagaggg cagagggttc tttgctctag 5641 ataaacaaac atcatctgcc tccagacact ggccacagta ggagtattgg tcctgggctt 5701 ccccagccac cagtcagcca caagctgtcg gtgacctatt ggtagaggga ctgggtgtga 5761 gggtctgggc cagggtgctt gacctgggag cagctggttc agagtccttc acaccgcagg 5821 ccagtaggga gcagtggaag ggacagtgct ccaggcattg ggaagtccct gctggctcta 5881 tcactcgggg caaacttctc cccacctggg ccttgggttc ttcagctata aaatggccag 5941 aggtgggggg cgggatgact aaaggaacag tgcagactcc cccactgtgg tcttgggagg 6001 ccagaggagt tagaagacct atctatctat ctatctatct acattgatca catcaaaagt 6061 atttatgtgc ctaacccggg gctggggatt gtggacgttc tggcctaatg gacagatgtg 6121 aactcatccc agagcatcgc aggaatgacc aggatgcccg ggaagagttg agctgagtgg 6181 gggctccagc cacagacagc ggcccaggcc agggagttgc tggcaacgaa ggagccagtg 6241 gtggaagaag aagaggccct gaatatacga ttgcctgccc acgttgtctt ctcttccata 6301 cacagtgaaa atgtagaaag atggtttgtg aggccaaact gtgaatgggc taaagggagg 6361 caaagttgca ctctccttcc ccagagggct caccaagagg gcacaccccc gggggttctg 6421 gtgggcaacg ggggtgagca tgtccctgcc ctggctccct ccatctgtga ccaggaggca 6481 tggctgggtg tatgttcagg tgaggctcag agtggcattg tgtccctgtc ccctgcccag 6541 ggcagtgagg ggagcccttg atgctgatta gaaggctaga actggggtag aggtgcctgg 6601 catgtctcat gccatgggga ctcaatctag caactgtgag tcctggggtc cctgtgatgg 6661 gaagagggca gtgccctgcc caatgtggca ggtgtcctca tggcaggatc tgcccctcac 6721 cagggggctg ggatctactt gcttggagct ctgagcaagg ccacaatgcc cgcccccacc 6781 cccaagtaga ctgcagcctg ggcctcatgg ggcttctccc aggcccacat ggcatccctc 6841 tctgagtttc caggccaccg tgggaccctg cagagcatct gcaccgggct ggatagggca 6901 gaaaagctca agggcagcta gcttgcctct tccctggaag aaaggtgctc tgggactcac 6961 caaccctgag aaagatagct ttcctggcca ccaccattcc ccaccaccct ggagaagcca 7021 attcccaggc ttgaagggca ctggctggca ggaggcctct tcattctgca ggaggtggaa 7081 aggacacctg tagacaggtg atgctcaccc ctcacctggc gccatggggc tgggaggtga 7141 gcggctggca tgtttgttcc tagggagcac catgtgagct taaggctccc ctgaccggcc 7201 ccaccacatg gcccagcctc ctagcacagc agcgctgacc tcagtgcagt ctgaggattg 7261 gaatccacca tgagatgatg tgagagctgt gtgccccagg atcaactttt tctccaactt 7321 ggccatcagc cagcgagttg ctaaggacct gagtcagcac tcacgttgcc tattcacact 7381 ccgcttgaaa gtccggaagg tggctactgc aaaatcaccc ctctgagaag tcctctctcc 7441 acatcttgtc cccctttgtg aagaccccta gttcgctctg cattttaggc atgaagagat 7501 acagcagggt gcgtccggag ggagctgtgg ccttgcaaca ccactggcaa cagggccggg 7561 gctcccggtg aaggtgtcag gaagtggaaa aggctggact ttgtctcctc tttgcctgct 7621 ggtagcctaa ccgcaaaagt atctctttat acagaatact tacagattct aatatatatt 7681 tgtatttcat tttgttacag tatttttata tgttaaagtc aacatccagc gtcttgtttt 7741 gcctttcaga tgctatgtgg tcgtggcacg ttttgttggg ggtttctgta gtcgtcttgt 7801 ttggatcaac tcctagaggc tggtttagaa caggcccatg agggagctgc acctgccctg 7861 gaagtattgt tttagactat gtcgatattg tctgttgtct tccatgtgaa catgacattg 7921 agtcactctg caaaaaaaaa aaaaaaaaa

One example of a nucleic acid sequence for human SPTAN1 is available as NCBI accession number NM_(—)001130438 (gi: 194595508). This sequence is recited below for easy reference as SEQ ID NO:165.

   1 gccactaccc gctgcggagt gaacggtgtg gagcggaggc cgcggaggct cctcggtcct   61 tcagcacccc tcggcccgac gcacccacgc ccctcacccc ccgagagccg aaaatggacc  121 caagtggggt caaagtgctg gaaacagcag aggacatcca ggagaggcgg cagcaggtcc  181 tagaccgata ccaccgcttc aaggaactct caacccttag gcgtcagaag ctggaagatt  241 cctatcgatt ccagttcttt caaagagatg ctgaagagct ggagaaatgg atacaggaaa  301 aacttcagat tgcatctgat gagaattata aagacccaac caacttgcag ggaaagcttc  361 agaagcatca agcatttgaa gctgaagtgc aggccaactc aggagccatt gttaagctgg  421 atgaaactgg aaacctgatg atctcagaag ggcattttgc atctgaaacc atacggaccc  481 gtttgatgga gctgcaccgc cagtgggaat tacttttgga gaagatgcga gaaaaaggaa  541 tcaaactgct gcaggcccag aagttggtgc agtacttacg agaatgtgag gacgtgatgg  601 actggatcaa tgacaaggaa gcaattgtta cttctgaaga gctgggccag gatctggagc  661 atgtagaggt tttacagaag aaatttgaag agtttcaaac agatatggct gctcatgaag  721 aaagagttaa tgaagtgaac cagtttgctg ccaaactcat acaggagcag caccctgagg  781 aggaactgat caagactaag caggatgaag tcaatgcagc ctggcagcgg ctgaagggcc  841 tggctctgca gaggcagggg aagctctttg gggcagcaga agttcagcgc tttaacaggg  901 atgtggatga gactatcagt tggattaagg aaaaggagca gttaatggcc tctgatgatt  961 ttggccgaga cctggcaagt gttcaggctc tgcttcggaa gcacgagggt ctggagagag 1021 atcttgctgc tctagaagac aaggtcaaag ccctgtgtgc tgaggctgac cgcctgcaac 1081 agtcccaccc tctgagtgca acacagattc aagtgaagcg agaggaactg attacaaact 1141 gggagcagat ccgcaccttg gcggcagaga gacatgcacg gctcaatgat tcatacaggc 1201 ttcaacgctt ccttgctgac ttccgtgacc tcaccagctg ggtgactgag atgaaagccc 1261 tcatcaatgc agatgagctt gccagtgatg tggctggggc tgaagccctg ctagatagac 1321 accaagagca caagggtgaa attgatgccc atgaagacag cttcaaatct gcagatgaat 1381 ctggacaggc actgcttgct gctggtcact atgcctcaga tgaagtgagg gagaagctga 1441 ccgtcctttc cgaggagaga gcggcgctgc tggagctgtg ggagctgcgc aggcagcagt 1501 acgagcagtg catggacctg cagctcttct accgggacac tgagcaggtg gacaactgga 1561 tgagcaagca ggaggcgttc ctgttgaatg aagacttggg agattccttg gatagtgtgg 1621 aagcgcttct taagaagcac gaagactttg agaaatccct tagtgcccag gaggaaaaga 1681 ttacagcatt agatgaattt gcaaccaagc taattcagaa caaccactat gcaatggaag 1741 atgtggccac tcgccgagat gctctgttga gccgccgcaa tgcccttcac gagagagcca 1801 tgcgtcgccg ggcccagcta gccgattctt tccatctgca gcagtttttc cgtgattctg 1861 atgagctcaa gagttgggtc aatgagaaga tgaaaactgc cacagatgaa gcttataaag 1921 atccatccaa cctacaagga aaagtacaga agcatcaggc ttttgaggct gagctctcag 1981 caaaccagag ccgaattgat gccttggaga aagctggcca aaagctgatt gatgtcaacc 2041 actatgccaa ggatgaagtg gcagctcgta tgaatgaggt gatcagtttg tggaagaaac 2101 tgctagaggc cactgaactg aaaggaataa agcttcgtga agccaaccag caacagcaat 2161 ttaatcgcaa tgttgaggat attgaattgt ggctatatga agtagaaggt cacttggctt 2221 cggatgatta cggcaaagat cttaccaatg tgcagaacct ccagaagaaa catgccctgc 2281 tagaggcaga tgtggctgct caccaggacc gaattgatgg catcaccatt caggcccgcc 2341 agttccaaga tgctggccat tttgatgcag aaaacatcaa gaagaaacag gaagccctcg 2401 tggctcgcta tgaggcactc aaggagccca tggttgcccg gaagcagaag ctggccgatt 2461 ctctgcggtt gcagcagctc ttccgggatg ttgaggatga ggagacgtgg attcgagaga 2521 aagagcccat tgccgcatct accaacagag gtaaggattt aattggggtc cagaatctgc 2581 taaagaaaca tcaagcctta caagcagaaa ttgctggaca tgaaccacgc atcaaagcag 2641 ttacacagaa ggggaatgcc atggtggagg aaggccattt tgctgcagag gatgtgaagg 2701 ccaagcttca cgagctgaac caaaagtggg aggcactgaa agccaaagct tcccagcgtc 2761 ggcaggacct ggaggactct ctgcaggccc agcagtactt tgctgatgct aacgaggctg 2821 aatcctggat gcgggagaag gaacccattg tgggcagcac tgactatggc aaggacgaag 2881 actctgctga ggctctactg aagaaacacg aagctttgat gtcagatctc agtgcctacg 2941 gcagcagcat ccaggctttg cgagaacaag cacagtcctg ccggcaacaa gtggccccca 3001 cggatgatga gactgggaag gagctggtct tggctctcta cgactatcag gagaagagtc 3061 cccgagaggt caccatgaag aagggagata tccttacctt actcaacagc accaacaagg 3121 attggtggaa agtggaagtg aacgatcgtc agggttttgt gccggctgcg tacgtgaaga 3181 aattggaccc cgcccagtca gcctcccggg agaatctcct ggaggagcaa ggcagcatag 3241 cactgcggca ggagcagatt gacaatcaga cacgcataac taaggaggcc ggcagtgtat 3301 ctctgcgtat gaagcaggtg gaagaactat atcattctct gctggaactg ggtgagaagc 3361 gtaaaggcat gttggagaag agttgcaaga agtttatgtt gttccgtgaa gcgaatgaac 3421 tacagcaatg gatcaatgag aaggaagccg ctctgacaag tgaggaggtc ggagcagact 3481 tggagcaggt tgaggtgctc cagaagaagt ttgatgactt ccagaaggac ctgaaggcca 3541 atgagtcacg gttgaaggac attaacaagg tagctgaaga cctggagtct gaaggtctca 3601 tggcagagga ggtgcaggct gtgcaacaac aggaagtgta tggcatgatg cccagggatg 3661 aaactgattc caagacagcc tccccgtgga agtctgctcg tctgatggtt cacaccgtgg 3721 ccacctttaa ttccatcaag gagctgaatg agcgctggcg gtccctacag cagctggccg 3781 aggaacggag ccagctcttg ggcagcgccc atgaagtaca gaggttccac agagatgctg 3841 atgaaaccaa agaatggatt gaagagaaga atcaagctct aaacacagac aattatggac 3901 atgatctcgc cagtgtccag gccctgcaac gcaagcatga gggcttcgag agggaccttg 3961 cggctctcgg tgacaaggta aactcccttg gtgaaacagc agagcgcctg atccagtccc 4021 atcccgagtc agcagaagac ctgcaggaaa agtgcacaga gttaaaccag gcctggagca 4081 gcctggggaa acgtgcagat cagcgcaagg caaagttggg tgactcccac gacctgcagc 4141 gcttccttag cgatttccgg gacctcatgt cttggatcaa tggaatacgg gggttggtgt 4201 cctcagatga gctagccaag gatgtcaccg gagctgaggc attgctggag cgacaccagg 4261 aacaccggac agaaatcgat gccagggctg gcactttcca ggcatttgag cagtttggac 4321 agcagctgtt ggctcacgga cactatgcca gccctgagat caagcagaaa cttgatattc 4381 ttgaccagga gcgtgcagac ctggagaagg cctgggttca gcgcaggatg atgctggatc 4441 agtgccttga actgcagctg ttccatcggg actgtgagca agctgagaac tggatggctg 4501 cccgggaggc cttcttgaat accgaagaca aaggagactc actggacagc gtagaggctc 4561 tgatcaaaaa acatgaagac tttgacaaag cgattaacgt ccaggaagag aagattgctg 4621 ctctgcaggc ctttgccgac cagctcatcg ctgccggcca ttatgccaag ggagacattt 4681 ctagccggcg caatgaggtc ttggacaggt ggcgacgtct gaaagcccag atgattgaga 4741 aaaggtcaaa gctaggagaa tctcaaaccc tccaacagtt cagccgggat gtggatgaga 4801 ttgaggcttg gatcagtgaa aaattgcaaa cagcgagtga tgagtcgtac aaggatccca 4861 ccaacatcca gctttccaag ctgctgagca agcaccagaa gcaccaggct tttgaagcag 4921 agctgcatgc caacgctgac cggatccgtg gggttatcga catgggcaac tccctcattg 4981 aacgtggagc ctgtgccggc agtgaggatg ctgtcaaggc ccgcctggct gccttagctg 5041 accagtggca gttcttggtg caaaagtcag cggaaaagag ccagaaactg aaagaagcca 5101 acaagcagca gaacttcaac acagggatca aggactttga cttctggctg tctgaggtgg 5161 aggccctgct ggcatccgaa gattatggca aagacctggc ttctgtgaac aacctgctga 5221 aaaagcatca actgctggaa gcagatatat ctgcccatga ggatcgcctg aaggacctga 5281 acagccaggc agacagcctg atgaccagca gtgccttcga cacctcccaa gtaaaggaca 5341 agagggacac catcaacggg cgcttccaga agatcaagag catggcggcc tcccggcgag 5401 ccaagctgaa tgaatcccat cgcctgcacc agttcttccg ggacatggat gacgaggagt 5461 cctggatcaa ggagaagaag ctgctggtgg gctcagagga ctacggccgg gacctaaccg 5521 gcgtgcagaa cctgaggaag aagcacaagc ggctggaagc agaactggct gcgcatgagc 5581 cggctattca gggtgtcctg gacactggca agaagctgtc cgatgacaac accatcggga 5641 aagaggagat ccagcagcgg ctggcgcagt ttgtggagca ctggaaagag ctgaagcagc 5701 tggcagctgc ccggggtcag cggctggaag agtccttgga atatcagcag tttgtagcca 5761 atgtggaaga ggaagaagcc tggatcaatg agaaaatgac cctggtggcc agcgaagatt 5821 atggcgacac tcttgccgcc atccagggct tactgaagaa acatgaagct tttgagacag 5881 acttcaccgt ccacaaggat cgcgtgaatg atgtctgcac caatggacaa gacctcatta 5941 agaagaacaa tcaccatgag gagaacatct cttcaaagat gaagggcctg aacgggaaag 6001 tgtcagacct ggagaaagct gcagcccaga gaaaggcgaa gctggatgag aactcggcct 6061 tccttcagtt caactggaag gcggacgtgg tggagtcctg gatcggtgaa aaggagaaca 6121 gcttgaagac agatgattat ggccgagacc tgtcttctgt gcagacgctc ctcaccaaac 6181 aggaaacttt tgacgctggg ctgcaggcct tccagcagga aggcattgcc aacatcactg 6241 ccctcaaaga tcagcttctc gccgccaaac acgttcagtc caaggccatc gaggcccggc 6301 acgcctccct catgaagagg tggagccagc ttctggccaa ctcagccgcc cgcaagaaga 6361 agcttctgga ggctcagagt cacttccgca aggtggagga cctcttcctg accttcgcca 6421 aaaaggcttc tgccttcaac agctggtttg aaaatgcaga ggaggactta acagaccccg 6481 tgcgctgcaa ctccttggaa gaaatcaaag ctttgcgcga ggcccacgac gccttccgct 6541 cctccctcag ctctgcccag gctgacttca accagctggc cgagctggac cgccagatca 6601 agagcttccg cgtagcctcc aacccctaca cctggtttac catggaggcc ctggaggaga 6661 cctggaggaa cctacagaaa atcatcaagg agagggagct ggagctgcag aaggaacagc 6721 ggcggcagga ggagaacgac aagctgcgcc aggagtttgc ccagcacgcc aacgccttcc 6781 accagtggat ccaagagacc aggacatacc tcctcgatgg gtcctgtatg gtggaagagt 6841 cggggaccct cgaatcccag cttgaagcta ccaaacgcaa gcaccaggaa atccgagcca 6901 tgagaagtca gctcaaaaag atcgaggacc tgggggccgc catggaggag gccctcatcc 6961 tggacaacaa gtacacggag cacagcaccg tgggcctcgc ccagcagtgg gaccagctgg 7021 accagctggg catgcgcatg cagcacaacc tggagcagca gatccaggcc aggaacacaa 7081 caggtgtgac tgaggaggcc ctcaaagaat tcagcatgat gtttaaacac tttgacaagg 7141 acaagtctgg caggctgaac catcaggagt tcaaatcttg cctgcgctcc ctgggctatg 7201 acctgcccat ggtggaggaa ggggaacctg accctgagtt cgaggcaatc ctggacacgg 7261 tggatccgaa cagagatggc catgtctcct tgcaagaata catggctttc atgatcagcc 7321 gcgaaactga gaacgtcaag tccagcgagg agattgagag cgccttccgg gccctcagct 7381 cagagggaaa gccttacgtg accaaggagg agctctacca gaacctgacc cgggaacaag 7441 ccgactactg cgtctcccac atgaagccct acgtggacgg caagggccgc gagctcccca 7501 ccgcgttcga ctacgtggag ttcacccgct cgcttttcgt gaactgagcc actccctggg 7561 tcacccaccc ctcgctgctt gccctgcgtc gccttgctgc atgtccgctc ctctgtgtgc 7621 tctcactttc cactgtaacc ttaagcctgc ttagcttgga ataagactta ggagaaaatg 7681 gtgcttcact aacccgcttc cggtccagtc acaatcatca tgtcactgtg gggacccaga 7741 tctgtgtctt gaagcagctg ccctcattcc gacttcagaa aatcgaagca gctggctcct 7801 ccccttgttc tctctcccac cctcccccaa atctgttttc atgtaaaaga caaataaatg 7861 atgacttccc ccaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 7921 aaaa

One example of a nucleic acid sequence for human TFCP2L1 is available as NCBI accession number NM_(—)014553 (gi: 212276201). This sequence is recited below for easy reference as SEQ ID NO:166.

   1 gggttcggag cgcgaagccg ccgctgggtc ctcggcgcgc cccgcgtctg cgcttgctgc   61 cgcgccccgg tcggcgcgct gggagttcca gccatgctct tctggcacac gcagcccgag  121 cactacaacc agcacaactc cggcagctac ctgcgtgatg tgctcgctct gcccatcttc  181 aagcaggagg aaccccagct gtcccccgag aacgaggccc gcctgccacc cctgcaatat  241 gtgttgtgtg ctgccacgtc cccagccgtg aagctgcatg aagagacgct gacctacctc  301 aaccaaggtc agtcttatga aatccgacta ctggagaatc ggaagctggg agactttcaa  361 gatctgaaca caaaatatgt caagagcatc atccgtgtgg tcttccatga ccgccggctg  421 cagtatacgg agcaccagca gctggagggc tggcggtgga gtcggccagg ggaccggatc  481 ctggacatcg atattccact gtctgttggt atcttggacc ccagggccag cccgacccag  541 ctgaatgcag tcgagttttt gtgggaccct gcgaagagag cttctgcatt cattcaggta  601 cactgcatca gcacagaatt cacccccagg aagcacgggg gcgagaaggg agtgcccttt  661 cgagtccaga ttgacacgtt taagcagaac gagaatgggg agtacacgga gcacctgcac  721 tcagccagct gccagatcaa ggtgttcaag ccgaagggag ccgatcggaa acagaagact  781 gaccgggaga agatggagaa aagaactgcc caagagaagg agaaatacca gccgtcctat  841 gaaaccacca tcctcacaga gtgctctcca tggcccgacg tggcctacca ggtgaacagc  901 gccccgtccc caagctacaa tggttctcca aacagctttg gcctcggcga aggcaacgcc  961 tctccgaccc acccggtgga ggccctgccc gtgggcagtg accacctgct cccatcagct 1021 tcgatccagg atgcccagca gtggcttcac cgcaacaggt tctcgcagtt ctgccggctc 1081 tttgccagct tctcaggtgc tgacttgctg aagatgtccc gagatgattt ggtccagatc 1141 tgtggtcccg cagatgggat ccggctcttc aacgccatca aaggccggaa tgtgaggcca 1201 aagatgacca tttatgtctg tcaggagctg gagcagaatc gagtgcccct gcagcagaag 1261 cgggacggca gtggagacag caacctgtct gtgtaccacg ccatcttcct ggaagagctg 1321 accaccttgg agctgattga gaagatcgcc aacctgtaca gcatctcccc ccagcacatc 1381 caccgagtct accggcaggg ccccacgggc atccatgtgg tggtgagcaa cgagatggtg 1441 cagaacttcc aagatgaatc ctgttttgtc ctcagcacaa ttaaagctga gagcaatgat 1501 ggctaccaca tcatcctgaa atgtggactc tgagcagcag tggacctcat acctgtctcc 1561 agctcccagc cctgtggatc cccgtggatg tagacattgc cccactgtaa gctgtggcct 1621 caccaggcaa gctgaggcca ggagggaccc tgcccagtct gtgaaagcta cagagcacca 1681 accagcagaa gcctgtggac accaagtacg gtgtacagaa agccagtggc tcctttctcc 1741 cttcctcttg gcctccagat tttgaatggt tccttgttct tttctattgg tccaaccctg 1801 acgttctaaa agggcaaaca gtggagacgt ctgctctgaa atccctcatc ccttagttgg 1861 aagctgattg ggtatcttgg tgctgcctgt attggtccct tctgaccact ctcctgcctc 1921 cagagaaagc tctgcttcac cctggaagct ggtaccttta cctcctcctc tgggagttgg 1981 ctgcatggcc agcactgccg acttgatggg agcagtttgc cctcattctc ctgtttcagg 2041 tttgcttccc ttctcagtga ccctggtgag catccgcctt tcctgttctt ggatgaattg 2101 atgggagtgg ggctattctg tgccttctac ctctttcttc tctacgttgt ttctaaggat 2161 ctgctgctgc ggaacccaaa gatgtgctcc tgtctctgca ctggcgcatt ggcatggtag 2221 atgccacaat gtatgtgcac ggcctttctc agagacatta gttctgaggc cctttgtggg 2281 gaggttaggg ggatggtaat agaaaaagac tattttattt cctggcaatc acgggtaagg 2341 aggattagga atgagtattc cattcctagg tgtcatcaga tgaccttgac caccacaata 2401 ccaggccctc ttggatggac ttatagaaag ttagagaaga ccttgttgaa ccgctgctaa 2461 acttgccaca ggagcgatgt gttttctctg agtgcccctc acttacatgt ttatctttgt 2521 ttgtagaggc tatgtttagg atattttgcc tgcatcagaa tgggtgcatc atctttctta 2581 atggcctaac tatcgggaaa tttgagtgtc agtaactgtg gtagactcag aaattcgtct 2641 ttgtcttgcc tctggttcct gggatccagt gatctctact ggcccagggc ttcagctctt 2701 ggttaattta ggttcatggg gaaccctctg accacctgaa tgggatgtca tagcttctaa 2761 atggagcttc tgtggaatga agtgctagac tgaaggacta ccagaataaa acagggtcta 2821 caatggggag aacttgtttt atagatgagg aaaccaaggc tcagaggggc aaagtcacct 2881 gcatggtagc acatagtgat agggtagcga tataaattta tcatataaac caggacatct 2941 cggaataaaa ggggctctgt tagtcattat gttgggtaat agccgtggca ttcctacaga 3001 acagagtgag gacaggctcc tgattcctct tccttcttta gaggagaagc ggggagtggg 3061 ttaactaaca gctttattga gatgtcattc acatgccatt cagtttaccc attgctagtg 3121 tccaattgta ttcacagaac caccatcaat tcacagaatt acagtcaacg ttggtacatt 3181 ttcatcaccc ccagtaaaac cccgtaccct tggtctgtca ctcctgcttt cctaactcct 3241 gcagtccaag gcagccatga atctactttc tatgtaagat taacctactc tggacatttc 3301 atatatctgg aatcatgtga tatctctttt gtgactggct tcttccactg aatgttttct 3361 agggccgtcc aagttgagga tgtatcagta cttcattctt ttgtattgct gaataatact 3421 tcattgtata gatagaccac atttgtttat tgattcatca gttgatggac atttgtgtgt 3481 ttttactttt tggctactct gaatgatgct gctatgaaca tatttctaca agattttgtg 3541 tggacatatg ttttcatttc ttttagcaat atacatagga gtggaattgc taggtcttac 3601 agtaactccg tgttttaact ttttgagaaa ctgccagact gttttctata gcagctgtac 3661 cattttacat tcccaccagc aatgtatcca ggtttcaatt tgtctacatc ctcatcaaca 3721 cttgctatta tctgtctttt tgcttttagc atcctaatga gtatgaaatg ctatcttgtg 3781 gttttgattt gcattcccct gatggcaact gatgctgagt gtcttttcct gtgcttacgg 3841 gccatgcgta tttctttgga gaaaggtcta tccaggtcct ttgcctattt ttaattgagt 3901 tgtctttttt tttttaagtt ttctgttttc ctaaccacta gactaccagg gatgagcctt 3961 ctttttatta ttgagttggg tgagctattt gtatattcta gacgccagtc ttttatcagg 4021 tatatgactg gtaaaaatgt tctccccttc tgtggattgt tttcagtttc ttgttggtgt 4081 cctttgagac acaaaacttt ttaactttga tgatttccaa gatacgtatt ttttttctat 4141 tgtcacttgt gcttttggtg ccatatctag aaaaccattg cctaatccaa ggtcaagaag 4201 attaatgcct gtgttttctt ctaagaacta tacttttagt tctcacaatg gtctttgatc 4261 catttcgagt atatttttat atatgatgtg atgtaggggt ccagcttcat tcttttgctt 4321 gtggatctcc acttgtccca ctgctgatta ttgagaaaaa tatcctttct ccacggaatt 4381 gtcttggcat ccttgctaaa ggcctctgct tcttactgga tcttctttcc tgggacatgg 4441 tgtcgttggg aagcttacct tttttttttt tttacttagt ctgtgtttgg ttccaccagt 4501 tttatgctgc ctttctactc tgttcttgct gtctccctct ttacctgagt caacggtact 4561 gagtcctatc tctctctgat gttccccagt cttccttggt gcatgttcta gctccacaca 4621 ctagtccttg gaggaaggtt gagaccaatg atttcctgtt atgagtcatg aggaaactga 4681 atcacctaga agtggaataa tgtgctcagg gtcaccatag cccattagtg gaaggaccag 4741 gactagacct ttagtcttct gaggtccagc cccttaggct gtctgtcatc actgtaccca 4801 agtgatgtca ctaccaaggc caaatgatgg tgggctaaat tttaattctc aaaagtgtag 4861 gaggctaata ttgtcttcta agttccaaaa gaagatgtaa taaaagtctg ttaccttaag 4921 tgtgctatta gtagagtctt ccatttttct ggcatgcccc tggcatctgc tcttcttacc 4981 ttctcgtggt tgtagttaaa gcttatagct tatgaaagaa tagaaaataa taaataccaa 5041 aaaaaagtac acatggtaat ttggtaccaa aatatctcag ctgcctaatt tagcagctca 5101 tcccttccac aggggtcaga tgagctaaag ctccaggttt tatttttcat ttgattgaca 5161 tacagaaaag ccatagccct tcccacagct gtccagggtc tttcctgtga gtccggaggt 5221 gctggcctat tgagcaggac agctcttccc agggcattcc caccaacctg tggcttctga 5281 actgtagctt ctttttacag tgaaccccag agggaaataa gacagacaca tgtgctcagg 5341 ccaccatctt gaactggaag cccaaagctg agttccttac tcttaggtcg tcacggtttt 5401 tgcggggtat ctgcaaggtt gagataaacc ctttcctgtt taccaggttg tcctttctgg 5461 atgaagggac agaggctgtt gaatggagga ataataggtt tgctggagga ggggcatggt 5521 atgcctgtgg aaaggacagg atggggtggg gaggtcgagg ctttgacttg gggtcctaaa 5581 caaaggtcag gtgttgccct agtgacctct tgcccagaca gcccagagcc ccttacacag 5641 agctattaac ctagggaagg ctttaccagc agtggactgg agccagccag ggtcacaagt 5701 ttccaagtcc agcattgctt caggggctgg cctgagtaac tgaagatctg aaaatcatta 5761 acaagtcgat gaaataaacg gaaaagcctc ttaggctgtt gtcagtggag cagagggaga 5821 aagtccctag gcgctcagag ggggtgagaa agcagtggat gattgggcgg gggtggggga 5881 ttagatgttg acactgcctg gggtgtagga agaggaacag agaacccaga gtcagggtcc 5941 tagatcccag accctcgctc agtatgagtc tctttgcctc tctgggtctc tatctcctcc 6001 tcttacaaat acaggcttgg tgatctctga agatggcacc aacctgccat gaaatgaatc 6061 tgaggggttt tcccattttt ccctccatca aaatcgtaca aaaagctgga cgtggtggcc 6121 catgcctcta atcctagcat tttgggaggc cgaggtggga gaatcacttg acgccaagag 6181 ttcgagacca gcctgggcat cgtagtgaga ctccatctct gtctttttga aaataaaaaa 6241 tctttgaaaa ttgcacaaca ggcaggagac ctttacgtgt gcccatcctg gttgtacaca 6301 gtgccaccag tgctcctgca gtgcaaggcg gcatgcttct tgacatgggt cagattgtgt 6361 ccatcgtgtc tttgggaatc agccctagct cctaactggg ctgactactt cctccgcaaa 6421 cttatggggg ctcccagata ttccttgcca gccaggggcc agacacagtg caggcacagt 6481 ctgtgtcatt ggtgcacatg tgcgtgttta catgtgtacc tgggttcctt cccttgccca 6541 tgaatttgcc atgagcacag ccagaagcag cctcagcttg gcaaggtgtg gagatgactg 6601 ctgttccctt cgcatttggg gaaaacaggc tccctcggta gctcgatgat cctcttttga 6661 tcttgtgtga cctcctggag agtggatgaa gctggtggcc ttagcttttc tagacagtgt 6721 aagtggcact gggcaaggcc cccagagcag ggcaaggtct ctagagcggg tctcccacat 6781 gactggcttc acacaggcac ttccgctcgg gttgcatgct ctgtgtcatc ttaccggtcc 6841 agggttgcag gtaggaaatg tttgtaccct cttctgattg ccacctcctt cccatcgccc 6901 cttagggaca gggcttgagg gccagtgagg cgctggtcag gcaccccagg cctccttggg 6961 acctgcccag gggcaccctg agagctcctg aaacccccac ttagcttcca gacctttctg 7021 caaaagctcc tcctggcttt cctccctccc ccaatctatg ggtcacagct aacagatctg 7081 agggcaactg ctgtgctagt ggccagggct gcacctgcca tccccggctc tgccacttta 7141 gggccttcta gaggcagtgt ccttaggaag tagctctgag gcatgggttt tctgctcctg 7201 tgcagggcag ctgatgggat aaggtgggga aggacggtca gtgcttgggc cccagctggc 7261 cagcctggcg atggggaaac caaaccatgt cccccagcga agggccagag tgggaacctg 7321 tcctcatgcc cttcgtcctg aggagccctg aggtgggcag caggggccag gggaagtttt 7381 caggccttca tcaaagagaa caacatcctc agctccgcac ccctcatcct gtatcagcac 7441 ttaccggtgt gtgactgccc ttgtcagcta gcatacggtg ggcccacctg gcccactggc 7501 tgtttatgcc actgatttat gatagggaat attatctttg aacccaatga agtgttttct 7561 cccccatcac aaaaaaaaaa attcttattt ttagtagaca tgtatttacc aaaaatatgt 7621 actcaattat tgtattttgg attttatcaa tttaaaaatt gtggaaattt gtttgctctt 7681 acgccaacat aatattgatt ttgcctcttg gctctgaaag cccaaaatat ttaccgtcta 7741 gcccgttaca gaaaaagtct gctgactact gagccagacc tccattacct ccatccctgt 7801 tggattattt aaagaaagcc tcagacagta agggcttttt taaaagaata aaatgacttg 7861 gtttgcgctt ggaagcaggg gaagcattca gatgagcggt ttctgcatta accctgccta 7921 tcacgcatct cgtgtcctgt gtggctggcg agcccccctt ggaaggttct ggtgcttcag 7981 ctggctcctg cagagtccac cccgcctcgt ggtgggaatg cagagccctt tgctttcctt 8041 cttgccgcct gcttcctgtt cctggggacc cgctgggcct ttggtctgca tcccctggcc 8101 aggtccctca gggttgatgc gtggagaagg actttgagca gtggtgggca gcagtggcct 8161 cctggccagc tcacactctt gtcctgggag gggcagcctg atctcacctc cacctagtac 8221 cttggggact gaggaccttt tggcttctct ggagcctgca agcctcttcc catgtgtcca 8281 gctgctcttc ctgctacaaa ggggactgct cacagtggcc tcagcttggt ggttttgagg 8341 ggccgccccc cggccctcca taagggtatc ctgggcctga gaattctgca tctgccattg 8401 gaggatggac agcctcaaat ggaaggagtc ccacgggaga tgggtccgag gtccggctgt 8461 ggccatccag ccccctgtgg cttgtccagc ctctgtgcac ccctggtgtc ttcactccag 8521 gggcagacag cagccactgc agttcctttc ttcgtgagta acagtagtga tagcagctgg 8581 ggctaacagg ctaggctttg tgttctgcgc atttggtcag cttctcactc gatcctccct 8641 aaagcaatgg ggaggccccc actagcccag ttttcaggaa gtcaactggg aggttagatg 8701 ggggccaggg tcccacagct actgatggcc cgagccaggt tgagcttcct ggtgtccagt 8761 ccggatccca cttgcagatc tcatgctctc agataggtgg gacaagttct tttgtcacag 8821 tgctggctct gtcctgaggc ctcattgctg gctgggtgtg ctctgctggg aaaagctttg 8881 cggggcttgc ttggttaacc acagaagaga aggggactgt ttggggtgcc tctctgcagc 8941 ctccccgtgc tgggtggaag cacggttact gtgttctcta atgttcatgt atttaaaatg 9001 atttctttct aaagatgtaa cctccacacc tttctccaga ttgggtgact cttttctaaa 9061 ggtggtggga gtatctgtcg gggtggtgtg gcccttggat gggtcaggtg ggtgtgagag 9121 gtcctgggga ggtgggcgtt gagctcaaag ttgtcctact gccatgtttt tgtacctgaa 9181 ataaagcata ttttgcactt gttactgtac catagtgcgg acgagaagtc tgtatgtggg 9241 atctgtgctt gggttagaat gcaaataaaa ctcacatttg taagaaaaaa aaaaaaaaaa 9301 aaaaaa

One example of a nucleic acid sequence for human TIAM1 is available as NCBI accession number NM_(—)003253 (gi: 115583669). This sequence is recited below for easy reference as SEQ ID NO:167.

   1 gccccgcatc gtgcccggcc ccgtcgcgga gatcccggac gaccgtcgcg ggttgatggt   61 cgcattccag atgtaaacag cttcagaagc ctgacggtca tatggtagaa tcactgtgga  121 ctgagaccca cctttctaga cctgaagccc aggaggagga agaggaggct ggttggtacc  181 atgggcataa tgctctgaat cctagtctct cacctagtat gtgagcagtc cctgcagatg  241 gcccatttgg agatcttgac aaagcctctt ctgtttccaa tggggttttt ggcgcattct  301 cacagactta gatgaaactg tgatggccac cgcagggggc aggtgctgac atcgtcccca  361 gccctgtggc tgttcatccg gacatcattt ccaacctcaa tatctaaatg ccacagtgct  421 cttggagcaa gttgggctgg ggaccactgt tgccttttaa gaccataaaa ccatgggaaa  481 cgcagaaagt caacatgtag agcacgagtt ttatggagaa aagcatgcca gcctggggcg  541 caagcacact tcccgctccc tgcgcctctc gcacaagacg cggaggacca ggcacgcttc  601 ctcggggaag gtgatccaca ggaactccga agtgagcacc cgatccagca gcacccccag  661 catcccccag tccctggctg aaaatggcct ggagcccttc tcccaagatg gtaccctaga  721 agacttcggg agccccatct gggtggaccg agtggacatg ggcttgagac ctgtgtctta  781 cactgactct tctgtcactc ccagcgtaga cagcagcatc gtcctcacag cagcctctgt  841 gcagagcatg ccagacactg aggagagcag gctttacggg gatgacgcta catatttggc  901 tgagggaggc aggaggcagc attcctatac atccaatggg cccactttca tggagacggc  961 gagctttaag aagaaacgct ccaaatctgc agacatctgg cgggaggaca gcctggaatt 1021 ctcactctct gatctgagcc aagaacattt aacaagcaac gaagaaatct tgggttccgc 1081 cgaagagaag gactgcgagg aggctcgggg gatggaaacg cgggcgagtc cgcggcagct 1141 cagcacctgt cagagagcca attccttggg tgacttgtat gctcagaaaa actctggagt 1201 gacagcaaac ggggggccgg ggagcaaatt tgcaggctac tgtcggaatt tggtgtctga 1261 tattcccaat cttgcaaacc ataagatgcc accagctgct gctgaagaga ctcctccgta 1321 cagtaattat aacacacttc cctgtaggaa atctcactgt ctctctgaag gtgccaccaa 1381 cccacaaatt agccatagca acagcatgca aggcagaaga gctaaaacaa ctcaggatgt 1441 taatgcaggc gagggcagtg agtttgcaga cagtgggatt gaaggggcca ctaccgacac 1501 ggacctcctg tccaggcgat ctaatgccac caactccagc tactcaccca ccacaggccg 1561 ggcctttgtg ggcagcgaca gcggcagcag ctccaccggg gatgcggctc gtcagggggt 1621 gtacgagaac ttccggcggg agctggagat gagcaccacc aacagcgaga gcctggagga 1681 ggccggctcg gcgcacagcg atgagcagag cagcggcacc ctgagctctc cgggccagtc 1741 ggacatcctg ctgaccgccg cacagggcac ggtgcgcaag gccggcgccc tggccgtcaa 1801 gaacttcctg gtgcacaaga agaacaagaa ggtggagtca gccacccgga ggaagtggaa 1861 gcactactgg gtgtccctga aaggatgcac gctatttttc tacgagagcg acggcaggtc 1921 tgggatagac cacaacagca tccccaaaca cgccgtctgg gtggagaaca gcattgtgca 1981 ggcggtgcct gagcacccca agaaggactt tgtcttctgc ctcagcaatt ccctgggtga 2041 tgccttcctt tttcagacca ctagccagac ggagcttgaa aactggatca ccgccatcca 2101 ctctgcctgc gccactgcgg tcgcgaggca ccaccacaag gaagacacgc tccgactcct 2161 gaaatcagag atcaaaaaac tggaacagaa gattgacatg gatgaaaaga tgaagaaaat 2221 gggtgaaatg cagctgtctt cagtcactga ctcaaagaaa aagaaaacaa tattagatca 2281 gatctttgtc tgggagcaaa atctcgagca gttccaaatg gacctgtttc gtttccgctg 2341 ttatttagcc agccttcagg gtggggagct gccaaacccc aaaaggcttc tcgcttttgc 2401 aagtcgacca acgaaagtgg ccatgggccg ccttggaatc ttttcggtat catcgtttca 2461 tgccctggtg gcagcacgca ctggtgaaac tggagtgaga agacgtactc aggccatgtc 2521 cagatccgcg agcaagcgaa ggagcaggtt ttcttctctg tggggtctgg atactacctc 2581 caaaaagaag cagggacggc caagcatcaa tcaggtgttt ggagagggaa ccgaagctgt 2641 aaagaaatct ttagagggaa tatttgatga cattgttcca gatggcaaga gggagaaaga 2701 agtggtctta cctaacgttc accagcacaa ccctgactgc gacatttggg tccacgagta 2761 tttcactcca tcctggttct gtctgcccaa taatcagcct gccctgacgg tcgtccggcc 2821 aggcgacact gcacgggaca ccctggagct gatttgcaag acacatcaac tggatcattc 2881 tgctcattac ctgcgcctga aatttctaat agaaaacaaa atgcagctct atgttccaca 2941 gcccgaggaa gacatctatg agctgctgta caaagaaatt gaaatctgtc caaaagtcac 3001 tcagagcatc cacattgaga agtcagatac agctgctgat acttacgggt tttcactttc 3061 ttctgtggaa gaagatggta ttcgaaggct gtacgtgaat agtgtgaagg aaaccggttt 3121 agcttccaag aaaggcctga aagcaggaga tgagattctt gagatcaata atcgtgctgc 3181 tgacgccctg aactcttcta tgctcaaaga tttcctctca cagccctcgc tgggcctcct 3241 ggtgaggacc taccccgagc tggaggaagg agtggagctg ctggaaagcc cgccccaccg 3301 agtggacggc cctgccgacc ttggcgagag ccccctcgcc tttctcacca gcaacccagg 3361 gcacagcctt tgcagcgagc agggcagcag tgctgagacc gctccagagg agaccgaggg 3421 gccagacttg gaatcctcag atgagactga tcacagcagc aagagtacag aacaggtggc 3481 cgcattttgc cgcagtttgc atgagatgaa cccctctgac cagagcccat ctcctcagga 3541 ctccacgggg cctcagctgg cgaccatgag acaactctcg gatgcagata agctgcgcaa 3601 ggtgatctgc gagctcctgg agacggagcg cacctacgtg aaggatttaa actgtcttat 3661 ggagagatac ctaaagcctc ttcaaaaaga aacttttctc acccaggatg agcttgacgt 3721 gctttttgga aatttaacgg aaatggtaga gtttcaagta gaattcctta aaactctaga 3781 agatggagtg agactggtac ctgatttgga aaagcttgag aaggttgatc aatttaagaa 3841 agtgctgttc tctctggggg gatcattcct gtattatgct gaccgcttca agctctacag 3901 tgccttctgc gccagccaca caaaagttcc caaggtcctg gtgaaagcca agacagacac 3961 ggctttcaag gcattcttgg atgcccagaa cccgaagcag cagcactcat ccacgctgga 4021 gtcgtacctc atcaagccca tccagaggat cctcaagtac ccacttctgc tcagggagct 4081 gttcgccctg accgatgcgg agagcgagga gcactaccac ctggacgtgg ccatcaagac 4141 catgaacaag gttgccagtc acatcaatga gatgcagaaa atccatgaag agtttggggc 4201 tgtgtttgac cagctgattg ctgaacagac tggtgagaaa aaagaggttg cagatctgag 4261 catgggagac ctgcttttgc acactaccgt gatctggctg aacccgccgg cctcgctggg 4321 caagtggaaa aaggaaccag agttggcagc attcgtcttc aaaactgctg tggtccttgt 4381 gtataaagat ggttccaaac agaagaagaa acttgtagga tctcacaggc tttccattta 4441 tgaggactgg gaccccttca gatttcgaca catgatcccc acggaagcgc tgcaggttcg 4501 agctttggcg agtgcagatg cagaggcaaa tgccgtgtgt gaaattgtcc atgtaaaatc 4561 cgagtctgaa gggaggccgg agagggtctt tcacttgtgc tgcagctccc cagagagccg 4621 aaaggatttc ctaaaggctg tgcattcaat cctgcgtgat aagcacagaa gacagctcct 4681 caaaaccgag agccttccct catcccagca atatgtccct tttggaggca aaagattgtg 4741 tgcactgaag ggggccaggc cggccatgag cagggcagtg tctgccccaa gcaagtctct 4801 tgggaggagg aggcggcggc tggctcgaaa caggtttacc attgattctg atgccgtctc 4861 cgcaagcagc ccggagaaag agtcccagca gccccccggt ggtggggaca ctgaccgatg 4921 ggtagaggag cagtttgatc ttgctcagta tgaggagcaa gatgacatca aggagacaga 4981 catcctcagt gacgatgatg agttctgtga gtccgtgaag ggtgcctcag tggacagaga 5041 cctgcaggag cggcttcagg ccacctccat cagtcagcgg gaaagaggcc ggaaaaccct 5101 ggatagtcac gcgtcccgca tggcacagct caagaagcaa gctgccctgt cggggatcaa 5161 tggaggcctg gagagcgcaa gcgaggaagt catttgggtt aggcgtgaag actttgcccc 5221 ctccaggaaa ctgaacactg agatctgact gcgtcacctg ccccgtagag aatgtgtgta 5281 gatacttcct gccctaactc tgcccaccct cctgtaccgt cgacaagaat gtccccttag 5341 gtcgcgctct tgcacacacg gttttggcag ctgacttggt tctgaagcca tgtagccacc 5401 caactttgtc attttcaaca acatcagaaa gaattgatca gaatcccaaa taagcttgag 5461 tcctatcttc tgtatattac taagggcttt tatttattct caataaatca gggcctgaac 5521 aattaaaaga aaaaagattc tatagcactg gaaagcaaat caccccagga gttaacggat 5581 gtacaacaga ttaatttaag ggatagtagc acacacacga tccttctatc tgaaatcagt 5641 ctcctagctg gggaaacctc tttcacacac aaaatgaaat gtgtacagct tgccgtgttc 5701 tgactgtacc cttccctctt ccatgtctga gaatctccgt gtattttaag aatgtgtgag 5761 gagagggtgg cgattcatgt ttcaatgagc ctcttttttt ttttccttcc tgttttggtc 5821 tatggctggt cttactctgt gtccatgttc ggaagctcta gttttgcata gaattataga 5881 gatgccaaac tctttgaaaa gagatccaaa tttatcgctt gagagaaaga aaagaaacac 5941 tattttttgt attttacctg agatacaggg gcacaaatag atgagaattt tacagtgtta 6001 gtgtatgtat ccctgagcct aaaaaatgag gatataacct tttacagaga gagtgaggcg 6061 tggtggtttt atatttatat atgaaaggcc agcaagctca tgcgaaggat atacttttct 6121 tccaaaaagc ggattttttt tttttaatgt ttgaatctat atttgagatg ggagtttggt 6181 tggattaaac atgacacccc ggtgggcggt gtgtgtgtct gttgcacatg gcagggaggg 6241 gagcctcctt ctcatggggt tgccatggtg atcattggtt tttccatcaa aattgcatct 6301 tcatccatag attaccttcc ccttccctga cagtccataa ccaaaccttt aaacagaaca 6361 acctctttaa aaacttctct tgtgtttaac actttcttca tgccaacgaa acagggtaaa 6421 catgctcaaa acattaacag tctaaacaga tatccaaata ctaagaagaa aaacaagtta 6481 tagcactttc aatttttttt ttttttttaa aaaaaggttt atagcttttt cttttcccat 6541 gtcacaatgt ccacttccta agaagggttt aaaatactat gaaaactttc tttttgggga 6601 aaatatctat ttggtgtttg acacatcagt aggtacttta aagacctgaa ttttatagta 6661 gctttaggag ttatatttta taaaaatcag ttatgacttt atatttccag acaatagaga 6721 gttcagtaca tcatgctctt gtgcctctgc ctgcttttcc tgcgttccca ccctgtattc 6781 cccccgcctt tcgggtttcc agggcttcga gcttgatctt ttgaaagttt tattctatta 6841 aatttttgct atatcttctg gttttctgaa aaagctttag aatggtttct ataccctttg 6901 tatcactgca tttttccata tcatctccgg ttcgatcgcg tccagatgga aaacggaagc 6961 agaggcttct aatcgtcgca tttactggct ccagtgcaac acatccatct gaaaacactc 7021 ggaagtctgg tgcttggaga gggtgccatt gtctcttgta cataaggtca tgacgtgtct 7081 atgtcaaaag ttcttatata tttcttttat aagctgaaag aaggtctatt tttatgtttt 7141 taggtctatg aatggaacgt tgtaaatgct tgtcaaacaa taaaaataac gaaaagtgaa 7201 aaaaaaaaaa aaaaaaaa

One example of a nucleic acid sequence for human TIMP1 is available as NCBI accession number NM_(—)003254 (gi: 73858576). This sequence is recited below for easy reference as SEQ ID NO:168.

  1 tttcgtcggc ccgccccttg gcttctgcac tgatggtggg tggatgagta atgcatccag  61 gaagcctgga ggcctgtggt ttccgcaccc gctgccaccc ccgcccctag cgtggacatt 121 tatcctctag cgctcaggcc ctgccgccat cgccgcagat ccagcgccca gagagacacc 181 agagaaccca ccatggcccc ctttgagccc ctggcttctg gcatcctgtt gttgctgtgg 241 ctgatagccc ccagcagggc ctgcacctgt gtcccacccc acccacagac ggccttctgc 301 aattccgacc tcgtcatcag ggccaagttc gtggggacac cagaagtcaa ccagaccacc 361 ttataccagc gttatgagat caagatgacc aagatgtata aagggttcca agccttaggg 421 gatgccgctg acatccggtt cgtctacacc cccgccatgg agagtgtctg cggatacttc 481 cacaggtccc acaaccgcag cgaggagttt ctcattgctg gaaaactgca ggatggactc 541 ttgcacatca ctacctgcag ttttgtggct ccctggaaca gcctgagctt agctcagcgc 601 cggggcttca ccaagaccta cactgttggc tgtgaggaat gcacagtgtt tccctgttta 661 tccatcccct gcaaactgca gagtggcact cattgcttgt ggacggacca gctcctccaa 721 ggctctgaaa agggcttcca gtcccgtcac cttgcctgcc tgcctcggga gccagggctg 781 tgcacctggc agtccctgcg gtcccagata gcctgaatcc tgcccggagt ggaagctgaa 841 gcctgcacag tgtccaccct gttcccactc ccatctttct tccggacaat gaaataaaga 901 gttaccaccc agcagaaaaa aaaaaaaaaa a

One example of a nucleic acid sequence for human TNS3 is available as NCBI accession number NM_(—)022748 (gi: 134152712). This sequence is recited below for easy reference as SEQ ID NO:169.

   1 agaatgggaa actgccttgg gagaagcccc aagtgagccc aagggcgcag agcagaagga   61 ccctggagtg taagagccta gattgcaagc ctggcaggag gagccggaag aattaacctc  121 gagtctgcac gcttttaaga acaaggcctt taaaaaatcc aaagtgtgtg gagtttgcaa  181 acaaattatt gacggtcaag gtatttcatg ccgagcctgc aagtattcct gccacaagaa  241 atgtgaagcc aaggtggtga ttccctgcgg tgtgcaagtc cgactggaac aggctccagg  301 gagttccacg ctgtccagtt ctctctgccg tgataaacct ctgcggcccg tcatcctgag  361 tcccaccatg gaggagggcc atgggctgga cctcacttac atcacggagc gcatcatcgc  421 tgtgtccttc cctgccggct gctctgagga gtcctacctg cacaacctac aggaggtcac  481 gcgcatgctc aagtccaagc acggggacaa ctacctggta ttaaaccttt cagaaaagag  541 atatgacctt acgaagctta acccaaagat catggatgtg ggctggccag agctccacgc  601 accgcccctg gataagatgt gtaccatatg caaggcgcag gagtcctggc tgaacagcaa  661 cctccagcat gtggtcgtca ttcactgcag gggcgggaaa ggacgcatag gagtggtcat  721 atcatcctac atgcatttca ccaacgtctc agccagcgcc gaccaggccc ttgacaggtt  781 tgcaatgaag aagttttatg atgacaaagt ttcagcttta atgcagcctt cccaaaaacg  841 gtatgttcag ttcctcagtg ggctcctgtc cggatcggtg aaaatgaatg cctctcccct  901 gttcctgcat tttgtcatcc tccacggcac ccccaacttc gacacaggtg gagtgtgccg  961 gccctttctg aagctctacc aagccatgca gcctgtgtac acctccggga tctacaacgt 1021 tggcccagaa aaccccagca ggatctgcat cgtcatcgag ccggcccagc ttctgaaggg 1081 agatgtcatg gtgaaatgct accacaagaa ataccgctcg gccacccgtg acgtcatttt 1141 ccgcctgcag tttcacactg gggctgtgca gggctacggg ctggtgtttg ggaaggagga 1201 tctggacaat gccagcaaag atgaccgttt tcctgactat gggaaggttg aattagtctt 1261 ctctgccagg cctgagaaga ttcaagggtc cgaacacttg tacaacgacc acggtgtgat 1321 tgtggactac aacacaacag acccactgat acgctgggac tcgtacgaga acctcagtgc 1381 agatggagaa gtgctacaca cgcagggccc tgtcgatggc agcctttacg cgaaggtgag 1441 gaagaaaagc tcctcggatc ctggcatccc aggtggcccc caggcaatcc cggccaccaa 1501 cagcccagac cacagtgacc acaccttgtc tgtcagcagt gactccggcc actctacagc 1561 ctctgccagg acggataaga cggaagagcg cctggcccca ggaaccagga ggggcctgag 1621 tgcccaggag aaggcagagt tggaccagct gctcagtggc tttggcctgg aagatcctgg 1681 aagctccctc aaggaaatga ctgatgctcg aagcaagtac agtgggaccc gccacgtggt 1741 gccagcccag gttcacgtga atggagacgc tgctctgaag gatcgggaga cagacattct 1801 ggatgacgag atgccccacc acgacctgca cagtgtggac agccttggga ccctgtcctc 1861 ctcggaaggg cctcagtcgg cccacctggg tcccttcacc tgccacaaga gcagccagaa 1921 ctcactccta tctgacggtt ttggcagcaa cgttggtgaa gatccgcagg gcaccctcgt 1981 tccggacctg ggccttggca tggacggccc ctatgagcgg gagcggactt ttgggagtcg 2041 agagcccaag cagccccagc ccctgctgag aaagccctca gtgtccgccc agatgcaggc 2101 ctatgggcag agcagctact ccacacagac ctgggtgcgc cagcagcaga tggttgtagc 2161 tcaccagtat agcttcgccc cagatgggga ggcccggctg gtgagccgct gccctgcaga 2221 caatcctggc ctcgtccagg cccagcccag agtgccactc acccccaccc gagggaccag 2281 cagtagggtg gctgtccaga ggggtgtagg cagtgggcca catccccctg acacacagca 2341 gccctctccc agcaaagcgt tcaaacccag gtttccagga gaccaggttg tgaatggagc 2401 cggcccagag ctgagcacag gcccctcccc aggctcgccc accctggaca tcgaccagtc 2461 catcgagcag ctcaacaggc tgatcctgga gctggatccc accttcgagc ccatccctac 2521 ccacatgaac gccctcggta gccaggccaa tggctctgtg tctccagaca gcgtgggagg 2581 tgggctccgg gcaagcagca ggctgcctga cacaggagag ggccccagca gggccaccgg 2641 gcggcaaggc tcctctgctg aacagcccct gggcgggaga ctcaggaagc tgagcctggg 2701 gcagtacgac aacgatgctg gggggcagct gcccttctcc aaatgtgcat ggggaaaggc 2761 tggtgtggac tatgccccaa acctgccgcc attcccctca ccagcggacg tcaaagagac 2821 gatgacccct ggctatcccc aggacctcga tattatcgat ggcagaattt taagtagcaa 2881 ggagtccatg tgttcaactc cagcatttcc tgtgtctcca gagacaccgt atgtgaaaac 2941 agcgctgcgc catcctccgt tcagcccacc tgagcccccg ctgagcagcc cagccagtca 3001 gcacaaagga ggacgtgaac cacgaagctg ccctgagacg ctcactcacg ctgtggggat 3061 gtcagagagc cccatcggac ccaaatccac gatgctccgg gctgatgcgt cctcgacgcc 3121 ctcctttcag caggcttttg cttcttcctg caccatttcc agcaacggcc ctgggcagag 3181 gagagagagc tcctcttctg cagaacgcca gtgggtggag agcagcccca agcccatggt 3241 ttccctgctg gggagcggcc ggcccaccgg aagtcccctc agcgctgagt tctccggtac 3301 caggaaggac tccccagtgc tgtcctgctt cccgccgtca gagctccagg ctcctttcca 3361 cagccatgag ctgtccctag cagagccacc ggactccctg gcgcctccca gcagccaggc 3421 cttcctgggc ttcggcaccg ccccagtggg aagtggcctt ccgcccgagg aggacctggg 3481 ggccttgctg gccaattctc atggagcgtc accgaccccc agcatcccgc tgacagcgac 3541 aggggctgcc gacaatggct tcctgtccca caactttctc acggtggcgc ctggacacag 3601 cagccaccac agtccaggcc tgcagggcca gggtgtgacc ctgcccgggc agccacccct 3661 ccctgagaag aagcgggcct cggaggggga tcgttctttg ggctcagtct ctccctcctc 3721 cagtggcttc tccagcccgc acagcgggag caccatcagt atccccttcc caaatgtcct 3781 tcccgacttt tccaaggctt cagaagcggc ctcacctctg ccagatagtc caggtgataa 3841 acttgtgatc gtgaaatttg ttcaagacac ttccaagttc tggtacaagg cggatatttc 3901 aagagaacaa gccatcgcca tgttgaagga caaggagccg ggctcattca ttgttcgaga 3961 cagccattcc ttccgagggg cctatggcct ggccatgaag gtggccacgc ccccaccttc 4021 agtcctgcag ctgaacaaga aagctggaga tttggccaat gaactcgtcc ggcacttttt 4081 gatcgagtgt accccgaagg gagtgcggtt gaaagggtgc tcgaatgaac catatttcgg 4141 gagcctgacg gccttggtgt gccagcattc catcacgccc ttggccttgc cgtgcaagct 4201 gcttatccca gagagagatc cattggagga aatagcagaa agttctcccc agacggcagc 4261 caattcagca gctgagctgt tgaagcaggg ggcagcctgc aatgtgtggt acttgaactc 4321 tgtggagatg gagtccctca ccggccacca ggcgatccag aaggccctga gcatcaccct 4381 ggtccaggag cctccacctg tgtccacagt tgtgcacttc aaggtgtcag cccagggcat 4441 caccctgaca gacaatcaga ggaagctctt cttccggagg cattaccccg tgaacagtgt 4501 gattttctgt gccttggacc cacaagacag gaagtggatc aaagatggcc cttcctcaaa 4561 agtctttgga tttgtggccc ggaagcaggg cagtgccacg gataatgtgt gccacctgtt 4621 tgcagagcat gaccctgagc agcctgccag tgccattgtc aacttcgtat caaaggtcat 4681 gattggttcc ccaaagaagg tctgagaact cccctccctc cctggaccca ccgatgcctc 4741 tcgaagccct ggagacagcc gttgggtgag ggtggggccc ccacttttta ccaaactagt 4801 aaacctgaca ttccaggccc atgaggggaa agaggatctt ccagctctgc aaaaacaaga 4861 acaaacaaca tcaccgtgaa ttggcctttc ctgaaagtga cttatctgac acatctctgt 4921 agccacatgc tttttgggta gaagaagctg ggcatgggtg caccccaccc cctagggtcc 4981 ccatgggaaa gggacatgca aggaaacagc acagaacacg aggtggtccc catgtccctg 5041 gcacactagc attccggggg atgaggaatc cccagccctt gaggcagagg tgccgagtga 5101 ctgccatgct tcgcccgtcc gcatgggcgc ttctgtccag ctgcacccga ggccgggggt 5161 ttccctcacc tcggtcttcc caagatggag atgctaacga aactgagaag ggggcgtatg 5221 tttgacgaag gtttgtgcaa gtcaggccct tctggaacac agcagggcct acaacgaggg 5281 gcctttgcga tgggctgtga ggatgggggt ggtgggaaga attggccacg ttggagaccc 5341 catgccaccc caccatggtg agtgctctgt gcctcctgct cacctgtggt gagctgggcg 5401 agctgggcga gctgggcgag ctgggctggg gagagcctgt gaggaccgag aggagaaatg 5461 agaagaagga acaaaaatat tatttctatg taatttatat tttacttatg ccaaattatt 5521 tatgataatt tgccattgct atactgtacc agtgtcaaat gctgcagcct gccaagctgt 5581 gattttgtga ggcttgtccc tatgtaggat gcaccgcagg cccctggcca ctgaaagagt 5641 gtgcagtgga ctgtgggtct cccatatgcg gtgccgccca aaggtggctt tgcctcaagc 5701 aacctaccct gatgttttac tcattggaat gtttttcccc gattgtggat gacttctttt 5761 ctgatggaga gagtccagga gggatggaaa actcctggat ttaagctcag catcccccac 5821 atgggctttt cgatcatctt caggcctgaa gctgcacgac ctgaagttcg cctgcattta 5881 tcagccctct ttgtgctgct ccttgccacc ttggggttcc tgctggggac catgtgtggt 5941 tgtggcatgt gtgagcagaa gggaggatga ggaaaaagag aagaaacccc ggtactgaca 6001 agctgttttt gagtgccact gtttgccatc atctaagcca ctgaatcaag tgtatttcag 6061 gcttatttca acattccaat gccctggttt tcctgcttga atctgttcgt ggtcaaaggt 6121 ttgggggaat ttgtgaccct ggaacatccc cagagtgaaa gatggagctg ggccacatca 6181 gaataaggcc ttggccccat cctctcacag cctaggtgct ctgcaggcat gctgactgtc 6241 ctgattgcga tccagcccga aattccctcc tctgctttca aaagtcaaat cccccattct 6301 taggccacac tggtgtcaca agctcctgtc agggagctgg ggtttgggaa tgtgctttgt 6361 gaactctgct ttaaagtgag gggccgagga aaacttagaa acaggcagag ttggaagcag 6421 ccaaatcaca gtgggtgttg tgtgtgtgtg cgtgtgtgca tgcgtgcgtg tatgcgtgtg 6481 tgaaagcagg tggaccattc cactttttag ctcctattga tgcaccaaac caagtgcctc 6541 atttctgtgc caaatgtttg ccttggtcgt tgtggacctc cttctctaac ttgcggtggc 6601 atgactgtca ggaggtgctg gcattttcag cagatcctca tgtgttgacc ctgatgtctt 6661 tagcagaggc ctctagcatc tcggtttttc atccactgca ggaatgtggc cacagggagc 6721 agaggtttgt actttcccca agaggtcctc atcctgagac ggtctctacc catgtttaac 6781 ccaaagagtg caggccaggt tccttatcct tctgatgaag gatgagagag ctcatttaga 6841 agtcagagca aactagggtc tcagtattga gaaacgcagc ctgccaggga atcacagaga 6901 catcggggtg cccgcgatgg ccctcatgaa gccatgcctc gacggcattc aggaagccct 6961 gcaaacgtgc tttttgaact cattggccag gtgtgatttt tacacaaggt aaacgtggtc 7021 aagggcatcg gggaatttgc tccaagcaga tagctccctc tgaggaacca aaggaagcaa 7081 gtttccacga tttctgaaga gctggtatag gaagtttctt tcttcctttt gtgttacatg 7141 tgcattaaac agaacaagct gtgtgtcatc acagattgta ctgtgggctc agaaaccgtg 7201 agagagcccc caccgtggac accggctcta gggccacagg aaaaggaacg tttccaggca 7261 ttttgtctcc agggctcccg ctggacaggc acgtactgcc ctggggagta aatgcggaga 7321 gttcacgaac tgtgcccaac gcatgttata gccagggtcc tactaactac tcagtaaaag 7381 aacgtattgt tgtattcctc cagtgttaag ctatagccat gttaaaagtc actgtgcatt 7441 tattctcagc atcaaatacc ttgtaacgtc ttctctgcct tgttagtgca tatttttact 7501 tttctgatac tgtaaagaat atatccagta tgtaaatgaa tgttctataa atcttttgta 7561 tagtcatttt ctctgctcct taaatatcat ctctattcag agtataataa aattatgaac 7621 ttggtaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 7681 aaaaaaaaaa aaaaaaa

One example of a nucleic acid sequence for human TSPAN12 is available as NCBI accession number NM_(—)012338 (gi: 48255911). This sequence is recited below for easy reference as SEQ ID NO:170.

   1 ggccctggct gccgccgctg cctcgtccgg actcggagag gacttgggag ggacagcggc   61 gctgggaggt ggcttagcag agactttcca gcaactgctg cccaggactt tttttttttt  121 ttttcttttt cccaggaggc ggcgacggcg gcggcggggg gagaggaaga gaaagaagcg  181 tctccagctg aagccaatgc agccctccgg ctctccgcga agaagttccc tgccccgatg  241 agcccccgcc gtgcgtcccc gactatcccc aggcgggcgt ggggcaccgg gcccagcgcc  301 gacgatcgct gccgttttgc ccttgggagt aggatgtggt gaaaggatgg ggcttctccc  361 ttacggggct cacaatggcc agagaagatt ccgtgaagtg tctgcgctgc ctgctctacg  421 ccctcaatct gctcttttgg ttaatgtcca tcagtgtgtt ggcagtttct gcttggatga  481 gggactacct aaataatgtt ctcactttaa ctgcagaaac gagggtagag gaagcagtca  541 ttttgactta ctttcctgtg gttcatccgg tcatgattgc tgtttgctgt ttccttatca  601 ttgtggggat gttaggatat tgtggaacgg tgaaaagaaa tctgttgctt cttgcatggt  661 actttggaag tttgcttgtc attttctgtg tagaactggc ttgtggcgtt tggacatatg  721 aacaggaact tatggttcca gtacaatggt cagatatggt cactttgaaa gccaggatga  781 caaattatgg attacctaga tatcggtggc ttactcatgc ttggaatttt tttcagagag  841 agtttaagtg ctgtggagta gtatatttca ctgactggtt ggaaatgaca gagatggact  901 ggcccccaga ttcctgctgt gttagagaat tcccaggatg ttccaaacag gcccaccagg  961 aagatctcag tgacctttat caagagggtt gtgggaagaa aatgtattcc tttttgagag 1021 gaaccaaaca actgcaggtg ctgaggtttc tgggaatctc cattggggtg acacaaatcc 1081 tggccatgat tctcaccatt actctgctct gggctctgta ttatgataga agggagccgg 1141 ggacagacca aatgatgtcc ttgaagaatg acaactctca gcacctgtca tgtccctcag 1201 tagaactgtt gaaaccaagc ctgtcaagaa tctttgaaca cacatccatg gcaaacagct 1261 ttaatacaca ctttgagatg gaggagttat aaaaagaaat gtcacagaag aaaaccacaa 1321 acttgtttta ctggacttgt gaatttttga gtacatacta tgtgtttcag aaatatgtag 1381 aaataaaaat gttgccataa aataacacct aagcatatac tattctatgc tttaaaatga 1441 ggatggaaaa gtttcatgtc ataagtcacc acctggacaa taattgatgc ccttaaaatg 1501 ctgaagacag atgtcatacc cactgtgtag cctgtgtatg acttttactg aacacagtta 1561 tgttttgagg cagcatggtt tgattagcat ttccgcatcc atgcaaacga gtcacatatg 1621 gtgggactgg agccatagta aaggttgatt tacttctacc aactagtata taaagtacta 1681 attaaatgct aacataggaa gttagaaaat actaataact tttattactc agcgatctat 1741 tcttctgatg ctaaataaat tatatatcag aaaactttca atattggtga ctacctaaat 1801 gtgatttttg ctggttacta aaatattctt accacttaaa agagcaagct aacacattgt 1861 cttaagctga tcagggattt tttgtatata agtctgtgtt aaatctgtat aattcagtcg 1921 atttcagttc tgataatgtt aagaataacc attatgaaaa ggaaaatttg tcctgtatag 1981 catcattatt tttagccttt cctgttaata aagctttact attctgtcct gggcttatat 2041 tacacatata actgttattt aaatacttaa ccactaattt tgaaaattac cagtgtgata 2101 cataggaatc attattcaga atgtagtctg gtctttagga agtattaata agaaaatttg 2161 cacataactt agttgattca gaaaggactt gtatgctgtt tttctcccaa atgaagactc 2221 tttttgacac taaacacttt ttaaaaagct tatctttgcc ttctccaaac aagaagcaat 2281 agtctccaag tcaatataaa ttctacagaa aatagtgttc tttttctcca gaaaaatgct 2341 tgtgagaatc attaaaacat gtgacaattt agagattctt tgttttattt cactgattaa 2401 tatactgtgg caaattacac agattattaa atttttttac aagagtatag tatatttatt 2461 tgaaatggga aaagtgcatt ttactgtatt ttgtgtattt tgtttatttc tcagaatatg 2521 gaaagaaaat taaaatgtgt caataaatat tttctagaga gtaaaaaaaa aaaaaaaaa

One example of a nucleic acid sequence for human UPP1 is available as NCBI accession number NM_(—)003364 (gi: 31742506). This sequence is recited below for easy reference as SEQ ID NO:171.

   1 ggtcagctga gttcgccggc ccagggcagg cggggcccga gcctagcggt aacccccggg   61 cagggcgggg ccgctcgcag actccatatg agattcacct cgcaggtggt tccctcattc  121 gagtgctccg gcgcacagac ccgcgccccg ccgtctgcga gcctcccgag agccgtccct  181 tcgtccggcc ctggagcatt gcgtttgtcg ccggtgtcgc agtgcgagga tggcgccgcg  241 ggtgtagcgg ctctctgcgc aggccgagtg ggcccagaga agcgaggaac tccgcagctc  301 gtcgacacgt ctcgtctcct gtcccaattc agggcttggt gaggtgactc gcggtcgcgg  361 gtgactcgcc ggcaggacac tgcctggaac gcctggagcg cctcccactg cagacgtctg  421 tccgcctcca gccgctctcc tctgacgggt cctgcctcag ttggcggaat ggcggccacg  481 ggagccaatg cagagaaagc tgaaagtcac aatgattgcc ccgtcagact tttaaatcca  541 aacatagcaa aaatgaaaga agatattctc tatcatttca atctcaccac tagcagacac  601 aatttcccag ccttgtttgg agatgtgaag tttgtgtgtg ttggtggaag cccctcccgg  661 atgaaagcct tcatcaggtg cgttggtgca gagctgggcc ttgactgccc aggtagagac  721 tatcccaaca tctgtgcggg aactgaccgc tatgccatgt ataaagtagg accggtgctg  781 tctgtcagtc atggtatggg cattccttct atctcaatca tgttgcatga gctcataaag  841 ctgctgtact atgcccggtg ctccaacgtc actatcatcc gcattggcac ttctggtggg  901 ataggtctgg agcccggcac tgtggtcata acagagcagg cagtggatac ctgcttcaag  961 gcagagtttg agcagattgt cctggggaag cgggtcatcc ggaaaacgga ccttaacaag 1021 aagctggtgc aggagctgtt gctgtgttct gcagagctga gcgagttcac cacagtggtg 1081 gggaacacca tgtgcacctt ggacttctat gaagggcaag gccgtctgga tggggctctc 1141 tgctcctaca cggagaagga caagcaggcg tatctggagg cagcctatgc agccggcgtc 1201 cgcaatatcg agatggagtc ctcggtgttt gccgccatgt gcagcgcctg cggcctccaa 1261 gcggccgtgg tgtgtgtcac cctcctgaac cgcctggaag gggaccagat cagcagccct 1321 cgcaatgtgc tcagcgagta ccagcagagg ccgcagcggc tggtgagcta cttcatcaag 1381 aagaaactga gcaaggcctg agcgctgccc tgcacctccg cagacctgct gtgatgactt 1441 gccattaaaa gcattgtcca aaatcccctg ttgtgtggac tttgagcaca ctttacacaa 1501 gaatctagaa aatcagatcg cgattaagag acagagaatc ttggattaac cgcatgggag 1561 atgttcttcc ttttgaagtt tcattggagc attttcaatg atgttagcct gatttggggt 1621 ttcttcaaga acattctacc aaatttttgt actatttcta gggaaatttt tcagacttta 1681 aaattctaat ggtagtcaga tttcatgtca ctaaacaaga aatctgacaa tagtgccagg 1741 aaactaattt cctgatacat taaaaaaatt ccatgcaaaa aaaaaaaaaa aaaaaa

One example of a nucleic acid sequence for human NAUK2 is available as NCBI accession number NM_(—)030952 (gi: 13569921). This sequence is recited below for easy reference as SEQ ID NO:172.

   1 gtgctttact gcgcgctctg gtactgctgt ggctccccgt cctggtgcgg gacctgtgcc   61 ccgcgcttca gccctccccg cacagcctac tgattcccct gccgcccttg ctcacctcct  121 gctcgccatg gagtcgctgg ttttcgcgcg gcgctccggc cccactccct cggccgcaga  181 gctagcccgg ccgctggcgg aagggctgat caagtcgccc aagcccctaa tgaagaagca  241 ggcggtgaag cggcaccacc acaagcacaa cctgcggcac cgctacgagt tcctggagac  301 cctgggcaaa ggcacctacg ggaaggtgaa gaaggcgcgg gagagctcgg ggcgcctggt  361 ggccatcaag tcaatccgga aggacaaaat caaagatgag caagatctga tgcacatacg  421 gagggagatt gagatcatgt catcactcaa ccaccctcac atcattgcca tccatgaagt  481 gtttgagaac agcagcaaga tcgtgatcgt catggagtat gccagccggg gcgaccttta  541 tgactacatc agcgagcggc agcagctcag tgagcgcgaa gctaggcatt tcttccggca  601 gatcgtctct gccgtgcact attgccatca gaacagagtt gtccaccgag atctcaagct  661 ggagaacatc ctcttggatg ccaatgggaa tatcaagatt gctgacttcg gcctctccaa  721 cctctaccat caaggcaagt tcctgcagac attctgtggg agccccctct atgcctcgcc  781 agagattgtc aatgggaagc cctacacagg cccagaggtg gacagctggt ccctgggtgt  841 tctcctctac atcctggtgc atggcaccat gccctttgat gggcatgacc ataagatcct  901 agtgaaacag atcagcaacg gggcctaccg ggagccacct aaaccctctg atgcctgtgg  961 cctgatccgg tggctgttga tggtgaaccc cacccgccgg gccaccctgg aggatgtggc 1021 cagtcactgg tgggtcaact ggggctacgc cacccgagtg ggagagcagg aggctccgca 1081 tgagggtggg caccctggca gtgactctgc ccgcgcctcc atggctgact ggctccggcg 1141 ttcctcccgc cccctcctgg agaatggggc caaggtgtgc agcttcttca agcagcatgc 1201 acctggtggg ggaagcacca cccctggcct ggagcgccag cattcgctca agaagtcccg 1261 caaggagaat gacatggccc agtctctcca cagtgacacg gctgatgaca ctgcccatcg 1321 ccctggcaag agcaacctca agctgccaaa gggcattctc aagaagaagg tgtcagcctc 1381 tgcagaaggg gtacaggagg accctccgga gctcagccca atccctgcga gcccagggca 1441 ggctgccccg ctgctcccca agaagggcat tctcaagaag ccccgacagc gcgagtctgg 1501 ctactactcc tctcccgagc ccagtgaatc tggggagctc ttggacgcag gcgacgtgtt 1561 tgtgagtggg gatcccaagg agcagaagcc tccgcaagct tcagggctgc tcctccatcg 1621 caaaggcatc ctcaaactca atggcaagtt ctcccagaca gccttggagc tcgcggcccc 1681 caccaccttc ggctccctgg atgaactcgc cccacctcgc cccctggccc gggccagccg 1741 accctcaggg gctgtgagcg aggacagcat cctgtcctct gagtcctttg accagctgga 1801 cttgcctgaa cggctcccag agcccccact gcggggctgt gtgtctgtgg acaacctcac 1861 ggggcttgag gagcccccct cagagggccc tggaagctgc ctgaggcgct ggcggcagga 1921 tcctttgggg gacagctgct tttccctgac agactgccag gaggtgacag cgacctaccg 1981 acaggcactg agggtctgct caaagctcac ctgagtggag taggcattgc cccagcccgg 2041 tcaggctctc agatgcagct ggttgcaccc cgaggggaga tgccttctcc cccacctccc 2101 aggacctgca tcccagctca gaaggctgag agggtttgca gtggagccct gagcagggct 2161 ggatatggga agtaggcaaa tgaaatgcgc caagggttca gtgtctgtct tcagccctgc 2221 tgaacgaaga ggatactaaa gagaggggaa cgggaatgcc cgcgacagag tccacattgc 2281 ctgtttcttg tgtacatggg ggggccacag agacctggaa agagaactct cccagggccc 2341 atctcctgca tcccatgaat actctgtaca catggtgcct tctaaggaca gctccttccc 2401 tactcattcc ctgcccaagt ggggccagac ctctttacac acacattccc gttcctacca 2461 accaccagaa ctggatggtg gcacccctaa tgtgcatgag gcatcctggg aatggtctgg 2521 agtaacgctt cgttattttt atttttattt ttatttattt atttattttt ttgagacgga 2581 gtttcgctct tggtgcccag gctagagtgc aatggcgcga tctcagctca cctcaacctc 2641 cgcctcccgg gttcaagcga ttctcctgcc tcagcctccc tagtagctgg gattacaggc 2701 gcccgccacc atgcccggct aattttgtat ttttagtaga gacagggttt ctccatgttg 2761 gtcaggctgg tctcaaactc ccgacctcag gtgatccacc cacctcggcc tcccaaagtg 2821 ctgggattac aggcgtgagc caccgcgccc cacctaaccc ttccttattt agcctaggag 2881 taagagaaca caatctctgt ttcttcaatg gttctcttcc cttttccatc ctccaaacct 2941 ggcctgagcc tcctgaagtt gctgctgtga atctgaaaga cttgaaaagc ctccgcctgc 3001 tgtgtggact tcatctcaag gggcccagcc tcctctggac tccaccttgg acctcagtga 3061 ctcagaactt ctgcctctaa gctgctctaa agtccagact atggatgtgt tctctaggcc 3121 ttcaggactc tagaatgtcc atatttattt ttatgttctt ggctttgtgt tttaggaaaa 3181 gtgaatcttg ctgttttcaa taatgtgaat gctatgttct gggaaaatcc actatgacat 3241 ctaagttttg tgtacagaga gatatttttg caactatttc cacctcctcc cacaaccccc 3301 cacactccac tccacactct tgagtctctt tacctaatgg tctctaccta atggacctcc 3361 gtggccaaaa agtaccatta aaaccagaaa ggtgattgga aaaaaaaaaa aaaaaaaaaa 3421 aaaaaaaaaa aaaaaaaaaa aaa

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All patents and publications referenced or mentioned herein are indicative of the levels of skill of those skilled in the art to which the invention pertains, and each such referenced patent or publication is hereby incorporated by reference to the same extent as if it had been incorporated by reference in its entirety individually or set forth herein in its entirety. Applicants reserve the right to physically incorporate into this specification any and all materials and information from any such cited patents or publications.

The specific methods and compositions described herein are representative of preferred embodiments and are exemplary and not intended as limitations on the scope of the invention. Other objects, aspects, and embodiments will occur to those skilled in the art upon consideration of this specification, and are encompassed within the spirit of the invention as defined by the scope of the claims. It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. The invention illustratively described herein suitably may be practiced in the absence of any element or elements, or limitation or limitations, which is not specifically disclosed herein as essential. The methods and processes illustratively described herein suitably may be practiced in differing orders of steps, and that they are not necessarily restricted to the orders of steps indicated herein or in the claims. As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to “a host cell” includes a plurality (for example, a culture or population) of such host cells, and so forth. Under no circumstances may the patent be interpreted to be limited to the specific examples or embodiments or methods specifically disclosed herein. Under no circumstances may the patent be interpreted to be limited by any statement made by any Examiner or any other official or employee of the Patent and Trademark Office unless such statement is specifically and without qualification or reservation expressly adopted in a responsive writing by Applicants.

The terms and expressions that have been employed are used as terms of description and not of limitation, and there is no intent in the use of such terms and expressions to exclude any equivalent of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention as claimed. Thus, it will be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.

The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

Other embodiments are within the following claims. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group. 

1. A method of detecting whether thyroid cancer cells are present in a test tissue or cell sample which comprises observing test levels of RNA or protein expression in the test tissue or cell sample for one or more differentially expressed genes; comparing the test levels of expression to one or more standard or control levels of expression, to ascertain whether higher or lower levels of expression of any of the differentially genes is present in the test tissue or cell sample; and thereby detecting whether thyroid cancer cells are present in the test tissue or cell sample; wherein the one or more differentially expressed genes are selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, PFAAP5, PGF, PIPS-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof.
 2. The method of claim 1, wherein the one or more differentially expressed genes are selected from the group consisting of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 and a combination thereof.
 3. The method of claim 1, wherein the one or more differentially expressed genes are selected from the group consisting of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIPS-E, PSD3, TNS3, TSPAN12, TIAM1 and a combination thereof.
 4. The method of claim 1, wherein the one or more differentially expressed genes are selected from the group consisting of C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 and a combination thereof.
 5. The method of claim 1, wherein the test levels of RNA expressed are detected by microarray analysis or by nucleic acid amplification.
 6. The method of claim 5, wherein the test levels of RNA expressed are detected by microarray analysis comprising use of one or more probes on the microarray that can hybridize to one or more of the differentially expressed genes, or an RNA or DNA copy of the one or more differentially expressed genes.
 7. The method of claim 6, wherein the one or more probes hybridize to any of SEQ ID NO:119-172.
 8. The method of claim 6, wherein the one or more probes hybridize to one or more of the differentially expressed genes, or an RNA or DNA copy of the one or more differentially expressed genes under moderate to highly stringent hybridization conditions.
 9. The method of claim 8, wherein the hybridization conditions are highly stringent hybridization conditions.
 10. The method of claim 5, wherein the nucleic acid amplification comprises reverse transcription polymerase chain reaction, real time polymerase chain reaction, and/or quantitative polymerase chain reaction.
 11. The method of claim 5, wherein the test levels of RNA expressed are detected by nucleic acid amplification using one or more primers that hybridize to one or more of the differentially expressed genes, or an RNA or DNA copy of the one or more differentially expressed genes under moderate to highly stringent hybridization conditions.
 12. The method of claim 11, wherein the hybridization conditions are highly stringent hybridization conditions.
 13. The method of claim 11, wherein the one or more primers hybridize to any of SEQ ID NO:119-172.
 14. The method of claim 11, wherein the one or primers are selected from the group consisting of SEQ ID NO:3-118.
 15. The method of claim 1, wherein the one or more standard or control levels of expression comprise: an expression level observed for a malignant thyroid cancer cell or tissue; an expression level observed for a benign thyroid cell or tissue; an expression level observed for a follicular adenoma with nuclear atypia; an expression level observed for a borderline thyroid cell or tissue; an expression level observed for a normal non-cancerous thyroid cell or tissue; or an expression level observed for a constitutively expressed gene.
 16. The method of claim 1, wherein the method can distinguish between benign, malignant and borderline thyroid cells or tissues.
 17. The method of claim 1, wherein the method can distinguish between benign thyroid cells or tissues, malignant thyroid cells or tissues, and follicular adenomas with nuclear atypia (FANA).
 18. The method of claim 1, wherein the test tissue or cell sample is obtained from a patient with thyroid cancer or suspected of having thyroid cancer.
 19. A kit comprising: (a) at least one set of oligonucleotide primers, wherein a first primer in the set contains a sequence complementary to a region in one strand of a nucleic acid sequence template and primes the synthesis of a first extension product, and a second primer contains a sequence complementary to a region in said first extension product and primes the synthesis of a nucleic acid strand complementary to said first extension product, and wherein the template is a differentially expressed gene, or an RNA or DNA copy of the differentially expressed gene; and (b) instructions for using the at least one set of oligonucleotide primers; wherein differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIOL, DPP4, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, PFAAP5, PGF, PIPS-E, PKNOX2, PRKACB, PROS1, PSD3, PSD3, QPCT, RAB27A, RAB27A, RXRG, SDC4, SERPINA1, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof.
 20. The kit of claim 19, wherein the differentially expressed gene is selected from the group consisting of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 and a combination thereof.
 21. The kit of claim 19, wherein the differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIPS-E, PSD3, TNS3, TSPAN12, TIAM1 and a combination thereof.
 22. The kit of claim 19, wherein the differentially expressed gene is selected from the group consisting of C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 and a combination thereof.
 23. The kit of claim 19, wherein the first primer and/or the second primer comprise a label.
 24. The kit of claim 19, comprising more than one set of primers.
 25. The kit of claim 19, wherein the first primer and/or the second primer hybridize to any of SEQ ID NO:119-172.
 26. The kit of claim 19, wherein the first primer and/or the second primer are selected from the group consisting of SEQ ID NO:3-118.
 27. The kit of claim 19, further comprising a container of nucleotides for use as subunits in the synthesis of and amplified product.
 28. The kit of claim 27, wherein one or more nucleotides further comprises a label.
 29. The kit of claim 27, wherein the nucleotides are deoxyribonucleotides.
 30. The kit of claim 19, wherein the instructions describe a method for amplifying an mRNA, cRNA or cDNA corresponding to the differentially expressed gene(s).
 31. The kit of claim 19, wherein the first primer and/or the second primer hybridize to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene under moderate to highly stringent hybridization conditions.
 32. The kit of claim 31, wherein the hybridization conditions are highly stringent hybridization conditions.
 33. A kit comprising (a) a microarray with covalently attached probes that can hybridize to a differentially expressed gene selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, PFAAP5, PGF, PIPS-E, PKNOX2, PRKACB, PROS1, PSD3, PSD3, QPCT, RAB27A, RAB27A, RXRG, SDC4, SERPINA1, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof; and (b) instructions for using the microarray.
 34. The kit of claim 33, wherein the differentially expressed gene is selected from the group consisting of DIOL, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 and a combination thereof.
 35. The kit of claim 33, wherein the differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, TIAM1 and a combination thereof.
 36. The kit of claim 33, wherein the differentially expressed gene is selected from the group consisting of C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 and a combination thereof.
 37. The kit of claim 33, wherein the probes hybridize to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene under moderate to highly stringent hybridization conditions.
 38. The kit of claim 33, wherein the hybridization conditions are highly stringent hybridization conditions.
 39. The kit of claim 33, wherein the probes hybridize to any of SEQ ID NO:119-172.
 40. The kit of claim 33, further comprising one or more standard or control probes.
 41. The kit of claim 33, where the one or more standard or control probes comprise a probe for a constitutively expressed gene.
 42. A method of detecting a mutation in a human BRAF gene comprising: (a) obtaining a test sample of genomic DNA from a human; (b) amplifying a segment of BRAF DNA from the genomic DNA using primers with SEQ ID NO: 1 and SEQ ID NO:2; and (c) detecting whether the mutation exists in the segment amplified; wherein the mutation consists of a glutamate substituted for valine at codon
 600. 43. The method of claim 42, further comprising detecting whether the human has thyroid cancer by observing test levels of RNA or protein expression in the test tissue or cell sample for any differentially expressed gene, and comparing the test levels of expression to one or more standard or control levels of expression, to ascertain whether higher or lower levels of expression of any of the genes is present in the test tissue or cell sample, and thereby detecting whether thyroid cancer cells are present in the test tissue or cell sample; wherein the differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, PFAAP5, PGF, PIPS-E, PKNOX2, PRKACB, PROS1, PSD3, PSD3, QPCT, RAB27A, RAB27A, RXRG, SDC4, SERPINA1, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof. 